Search

To examine the effect of Shenmai Injection (SMJ) on ferroptosis during myocardial ischemia reperfusion (I/R) injury in rats and the underlying mechanism.A total of 120 SPF-grade adult male SD rats, weighing 220-250 g were randomly divided into different groups according to a random number table. Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion. SMJ was injected intraperitoneally at the onset of 120 min of reperfusion, and erastin (an agonist of ferroptosis), ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) and ML385 (an inhibitor of nuclear factor erythroid-2 related factor 2 (Nrf2)) were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments. Cardiac function before ischemia, after ischemia and after reperfusion was analysed. Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed, and the myocardial infarction area was measured. Additionally, the concentration of FeCompared with the sham group, I/R significantly injured heart tissues, as evidenced by the disordered, ruptured and oedematous myocardial fibres; the increases in infarct size, serum CK-MB, cTnI and MDA levels, and myocardial FeFerroptosis is involved in myocardial I/R injury. Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis, thereby providing a strategy for the prevention and treatment of ischemic heart diseases.

Diabetes mellitus is a metabolic disease with a high prevalence worldwide, and cardiovascular complications are the leading cause of mortality in patients with diabetes. Diabetic cardiomyopathy (DCM), which is prone to heart failure with preserved ejection fraction, is defined as a cardiac dysfunction without conventional cardiac risk factors such as coronary heart disease and hypertension. Mitochondria are the centers of energy metabolism that are very important for maintaining the function of the heart. They are highly dynamic in response to environmental changes through mitochondrial dynamics. The disruption of mitochondrial dynamics is closely related to the occurrence and development of DCM. Mitochondrial dynamics are controlled by circadian clock and show oscillation rhythm. This rhythm enables mitochondria to respond to changing energy demands in different environments, but it is disordered in diabetes. In this review, we summarize the significant role of circadian clock-controlled mitochondrial dynamics in the etiology of DCM and hope to play a certain enlightening role in the treatment of DCM.

Background and Objectiv: Dizziness is a common complication of gastrointestinal endoscopy under general anesthesia. Dizziness is primarily caused by a lack of energy and blood volume following fasting and water deprivation. Hypertonic glucose solution (HGS) is an intravenous energy replenishment, that increases blood volume due to its hyperosmotic characteristics and can be directly absorbed from blood circulation. This study aimed to HGS can prevent dizziness after gastrointestinal endoscopy. Methods: This was a double-blind, randomized, controlled study. Eligible patients were randomly allocated into two groups based on the intravenous agent administered before gastrointestinal endoscopy: Group A, saline (0.9%; 20 mL); and group B, HGS (50%; 20 mL). Overall, 840 patients were included in the statistical analysis. The scores and incidence of dizziness were assessed. Results: The dizziness score were higher in group A than in group B (1.92 ± 0.08 vs. 0.92 ± 0.06; p < 0.01). The incidence of mild dizziness and moderate-to-severe dizziness was significantly lower in group B than in group A (40.10% vs. 51.78% and 3.10% vs. 19.72%, respectively; p < 0.01). The incidence and score of dizziness were significantly lower in males than in females (30.81% vs 51.82% and 0.64 ± 0.08 vs 1.12 ± 0.08, respectively; p < 0.01) after pretreatment with HGS. Conclusion: Pretreatment with HGS effectively prevents dizziness after gastrointestinal endoscopy under general anesthesia. The mechanism of action is unclear but might be related to body energy replacement and an increase in blood volume following HGS administration. The registration number: ChiCTR1900020887

The complex progression of type-2 diabetes (T2DM) results in inconsistent findings on myocardial susceptibility to ischemia-reperfusion (IR). IR injuries in multiple organs interconnect with ferroptosis. Targeting Rev-erbs might limit ferroptosis, with increasing attention turning to the application of circadian medicine against IR injuries. However, whether the Rev-erbs agonist SR9009 could mitigate diabetic IR injury remains unknown. Here, we investigated the susceptibility to IR at onset of T2DM in rats and its potential association between SR9009 and ferritinophagy/ferroptosis signaling. Onset of T2DM model was induced with a high-fat diet and the intraperitoneal injection of a low dose of streptozotocin. Myocardial IR model was established as well. Rats' general characteristics, cardiac function, glycolipid profiles, serum biochemistry, apoptosis index (AI) and morphological histology were observed and analyzed. Western blot and immunofluorescence (IF) were employed to evaluate the expression of ferritinophagy/ferroptosis signaling and its co-localization. Glycolipid profiles and cardiac diastolic function were significantly impaired in diabetic rats. CK-MB, AI levels and ferritinophagy/ferroptosis-related proteins expression decreased towards myocardial IR in diabetic rats compared to non-diabetic rats'. The ferroptosis inducer Erastin up-regulated SOD, MDA, and AI levels, as well as the expression of ferritinophagy/ferroptosis-related proteins in diabetic rats towards IR. Treatment with SR9009 down-regulated the degree of myocardial injury and ferritinophagy/ferroptosis-related proteins expression compared to diabetic rats treated with or without Erastin. Onset of T2DM activated endogenous cardioprotection against the susceptibility to myocardial IR injury, and SR9009 exogenously enhanced this endogenous mechanism and alleviated myocardial IR injury at onset of T2DM by down-regulating ferritinophagy/ferroptosis signaling.

Background Ischemic post-conditioning (IPO) is a strategy in reducing myocardial ischemic-reperfusion (I/R) injury, but its specific molecular mechanism is incompletely understood. Deletions or mutations in the DJ-1 gene are directly linked to the cardiovascular system. DJ-1 plays a critical role in regulating mitochondrial homeostasis in response to stress through translocation of DJ-1 from the cytoplasm into the nucleus. Meanwhile, how the DJ-1 is removed in myocardial I/R injury and regulating apoptosis is needed to further verified. Given the discovery mentioned above, we hypothesize that DJ-1 translocate to mitochondria recover IPO induced cardioprotection in STZ-induced diabetic rats. To evaluate our hypothesis, we overexpressed the DJ-1 protein under high glucose condition, subjected IPO or not. And then measure the expression of DJ-1 in mitochondria and cytoplasm after myocardial I/R. Results We found that DJ-1 translocated to mitochondria combined with Bcl-xL was reduced cardiomyocyte injury and apoptosis in diabetic myocardial I/R heart. Additionally, the binding of DJ-1 and Bcl-xL is dependent on the oxidative state of DJ-1(oxidation of DJ-1 at Cys-106 is important for its protective effect). Conclusions If our hypothesis is correct, promote DJ-1 mitochondrial transfer may be critical with respect to restoring myocardial responsiveness to IPO in diabetes.

Background: Diabetic myocardial ischemia reperfusion (MI/R) injury is aggravated after myocardial infarction, which leads to myocardial damage. Molecular mechanisms associated with the diabetic ischemia-related cardiac diseases are not yet fully understood. Nogo-A is an endoplasmic reticulum (ER) protein ubiquitously expressed in tissues including in the heart. However, the mechanisms that account for the Nogo-A in MI/R injury remain unknown. Methods: SD (Sprague Dawley) rats were subjected to 45 min of ischemia, followed by 3 h reperfusion. Rats were injection with streptozotocin (60mg/kg), tauroursodeoxycholic acid injection (100mg/kg) or corresponding controls just prior to MI/R. Blood and heart samples were collected at 3 h post-reperfusion. Serum LDH and CK-MB, myocardial infarct size, histopathologic changes, apotosis and ER stress were analyzed to evaluate MI/R injury. Signaling pathways were also investigated in vitro using embryonic rat cardiomyocyte-derived H9c2 cells cultures to identify underlying mechanisms for Nogo-A in diabetic MI/R injury. Results: TUDCA treatment significantly reduced Nogo-A, GRP78 and CHOP levels, diminished myocardial infarct areas, attenuated ER stress and decreased myocardial apoptosis after MI/R. ER stress signaling was significantly decreased in the TUDCA-treated MI/R group compared with controls. The effect of Nogo-A was abrogated by pretreatment with knockdown CHOP. A positive feedback loop between Nogo-A and CHOP was found leading to an enhanced ER stress in diabetic MI/R injure. Conclusions: Our data suggest that Nogo-A mediated ER stress plays a major role in diabetic MI/R injury and Nogo-A might be a key regulator of ER stress.

Background: COVID-19 continues to spread globally and results in additional challenges for perioperative management in parturients. The purpose of this study was to determine the incidence and identify associated factors for neuraxial anaesthesia-related hypotension in COVDI-19 parturients during caesarean delivery.Methods: We performed a multicenter case-control study at 3 medical institutions in Hubei province, China form 1th January to 30th May 2020. All ASA Physical Status II full termed pregnant women who received caesarean delivery under neuraxial anaesthesia were eligible for inclusion. The univariate analysis and binary logistic regression analysis were used to identified the independent predictors of neuraxial anaesthesia-related hypotension.Results: Present study included 102 COVID-19 parturients. The incidence of neuraxial anaesthesia-related hypotension was 58%. Maternal abnormal lymphocyte count (OR = 3.41, p = 0.03), full stomach (OR = 3.22, p = 0.04), baseline heart rate (OR = 1.04, p = 0.03), experience of anaesthetist (OR = 0.86, p = 0.02) and surgeon (OR = 0.76, p = 0.03), and combined spinal-epidural anaesthesia technique (OR = 3.27, p = 0.02) were associated with neuraxial anaesthesia-related hypotension. The area under the receiver operating characteristic curve achieved 0.83 which was significantly higher than 0.5 (p < 0.001). And the sensitivity, specificity and percentage correct were 75%, 79% and 75%, respectively. The Hosmer-Lemeshow test showed a good calibration of the model (H = 2.01, DF = 8, p = 0.98).Conclusions: Maternal abnormal lymphocyte count, full stomach, baseline heart rate, experience of anaesthetist and surgeon, and combined spinal-epidural anaesthesia technique were identified as the independent predictors of neuraxial anaesthesia-related hypotension.

Circadian rhythms are fundamental to regulating metabolic processes and cardiovascular functions. Phosphorylated PERIOD2 (PER2) is a key factor in determining the period of the mammalian circadian clock. Moreover, casein kinase 1ε (CK1ε) primes the PER2 phosphoswitch and its stability. While diabetes contributes to the disorder of the circadian system, changes in PER2 forms and their regulatory mechanisms during diabetes remain unclear. In this study, we examined the impact of diabetes on PER2 and CK1ε signaling in the heart to determine the potential mechanism between them.A Type-1 diabetic rat model was established by intraperitoneally injecting rats with streptozotocin. General characteristics, cardiac function, histology, serum biochemistry, apoptosis index and circadian rhythm were analyzed in controls and diabetic rats treated with or without PF-670462 (a CK1ε inhibitor). A high-glucose model was created with H9c2 cells and treated with PF-670462 and PER2 siRNA. Cell viability, LDH release, dead/live rate and histology were determined to assess cellular injuries. RT-PCR and Western blot were used to evaluate the expression of PER2, CK1ε, phosphorylated PER2, and immunofluorescence (IF) was employed to determine PER2's location.STZ-induced diabetes prolonged PER's period and upregulated the expression of CK1ε and phosphorylated PER2 compared to the controls. Inhibiting CK1ε and PER2 with PF-670462 downregulated the phosphorylation at Ser662 and the nuclear entry of PER2 in high glucose conditions. In addition, pharmacologically or genetically suppressing PER2 mitigated high-glucose-instigated myocardial injury.Diabetes compromised PER2 in association with activated CK1ε signaling. Targeting CK1ε-regulated PER2 alleviates myocardial injuries in the presence of high glucose.

Background: Circadian clock has been closely related to the development of diabetes mellitus and cardiovascular disease; the disruption of circadian clock exacerbates myocardial ischemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop by recruitmenting the expression pattern of circadian nuclear receptor Rev-erbα, then to maintain the stability of circadian gene such as BMAL1. In this research, we explored the mechanism of HDAC3-orchestrated Rev-erbα/BMAL1 pathway in increasing MI/RI vulnerability of diabetes, and its relationship with mitophagy.Methods and results: Streptozocin (STZ) was used to establish type 1 diabetes by intraperitoneal injection. After 8 weeks, the diabetic and non-diabetic rats were exposed to MI/RI by ligating the left anterior descending coronary artery (LDA) for 30 minutes and reperfusion for 120 minutes at four time points of zeitgeber (ZT) 0, 6, 12 and 18. Circadian clock gene oscillations were rapidly attenuated in diabetic I/RI hearts, versus sham and/or the non-diabetic I/RI hearts, in accord with circadian mitophagy. By utilizing AAV-HDAC3 to knockdown HDAC3 expression, HDAC3 deficiency significantly attenuated diabetic MI/RI associated with increased autophagy activation. In vitro experiments, primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA exposed to hypoxia/reoxygenation (H/R). The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high glucose condition with decreased BMAL1 expression and autophagy level. After H/R stimulation, the cell injury was obviously increased with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 level. Moreover, high glucose aggravated H/R injury compared with low glucose by reducing autophagy level, increasing the levels of HDAC3 and Rev-erbα and down-regulating BMAL1 expression. HDAC3 and Rev-erbα siRNA can alleviate high glucose and H/R-induced injury by up-regulating BMAL1 expression and mitophagy levels.Conclusion: These findings suggest that in diabetic rat MI/RI , the circadian clocks were rapidly impaired then to inhibit mitophagy; cardiac-targeted manipulation of HDAC3-orchestrated Rev-erbα/BMAL1 pathway may be the mechanism of the decreased toleration to ischemia with a circadian dependent variability.

Dexmedetomidine (DEX), a potent and highly selective agonist for α

Diabetic hearts are more susceptible to myocardial ischemia/reperfusion (I/R) injury and less sensitive to ischemic postconditioning (IPostC), but the underlying mechanisms remain unclear. PKCβ2 is preferentially overactivated in diabetic myocardium, in which autophagy status is abnormal. This study determined whether hyperglycemia-induced PKCβ2 activation resulted in autophagy abnormality and compromised IPostC cardioprotection in diabetes. We found that diabetic rats showed higher cardiac PKCβ2 activation and lower autophagy than control at baseline. However, myocardial I/R further increased PKCβ2 activation and promoted autophagy status in diabetic rats. IPostC significantly attenuated postischemic infarct size and CK-MB, accompanied with decreased PKCβ2 activation and autophagy in control but not in diabetic rats. Pretreatment with CGP53353, a selective inhibitor of PKCβ2, attenuated myocardial I/R-induced infarction and autophagy and restored IPostC-mediated cardioprotection in diabetes. Similarly, CGP53353 could restore hypoxic postconditioning (HPostC) protection against hypoxia reoxygenation- (HR-) induced injury evidenced by decreased LDH release and JC-1 monomeric cells and increased cell viability. These beneficial effects of CGP53353 were reversed by autophagy inducer rapamycin, but could be mimicked by autophagy inhibitor 3-MA. It is concluded that selective inhibition of PKCβ2 could attenuate myocardial I/R injury and restore IPostC-mediated cardioprotection possibly through modulating autophagy in diabetes.

Objective In this study, the neuroprotective mechanism of 2-arachidonoylglycerol 2-AG against non-caspase-dependent apoptosis in mice hippocampal neurons following MCAO was investigated. Method One hundred and fifty healthy clean male C57BL/6 mice were randomly divided into 3 groups: sham group, model group and 2-AG treatment group, 50 mice in each group. A modified Zea Longa method was used to establish a model of middle cerebral artery occlusion (MCAO) in mice. The apoptosis rate and mitochondrial membrane potential of hippocampal nerve cells were measured by flow cytometry. The mRNA expressions of AIF, Endo G and BNIP3 in hippocampal tissues were determined by qPCR. Western blot was used to determine the protein expressions of AIF, Endo G and BNIP3 in the mitochondria of hippocampal tissue. Results The apoptosis rate of hippocampal neurons in the group treated with 2-AG was significantly lower than that of the model (P

To observe the influence of therapy with Chinese medicine Lirukang Granule (利乳康颗粒, LRKG) combined with psychological intervention on anxiety states and sex hormones in patients with cyclomastopathy and menoxenia. A total of 470 subjects were randomly assigned to three groups by the net-central randomization system, the treatment group (161 patients, treated with LRKG and psychological intervention), the Chinese medicine group (157 patients, treated with LRKG), and the psychological intervention group (152 patients, treated with psychological intervention). The dose of LRKG was 12 g three times per day; psychological intervention included establishing relations, cognitive intervention and psychological persuasion, 30–40 min per session, once a week. The therapy duration for all groups was three months. The efficacy was compared and anxiety state/State-Trait Anxiety Invertory (STAI) scoring was measured before and after treatment. The serum estradiol (E2), progesterone (P), prolactin (PRL) and follicle stimulating hormone (FSH) levels of 60 patients selected randomly from each group during the luteal phase were measured before and after treatment, and a group of 20 healthy women were evaluated for comparison. A follow-up was arranged for one year after treatment. Thirty subjects were lost to follow-up. (1) Comparison of efficacy: the markedly effective rate and the total effective rate of the treatment group were 86.67% (131/150) and 98.00% (147/150), respectively; of the Chinese medicine group, 64.58% (93/144) and 90.27% (130/144), respectively; and of the psychological intervention group, 0% (0/146) and 3.42% (5/146), respectively. The markedly effective rate and the total effective rate in the treatment group were significantly higher than those in the Chinese medicine and psychological intervention groups (P

Long non-coding (lncRNA) MALAT1 can be increased by hypoxia or ischemic limbs. Also, downregulation of MALAT1 contributes to reduction of cardiomyocyte apoptosis. However, the functional involvement of MALAT1 in myocardial ischemia-reperfusion (I/R) injury has not been defined. This study investigated the functional involvement of lncRNA-MALAT1 in cardioprotective effects of fentanyl. HL-1, a cardiac muscle cell line from the AT-1 mouse atrial cardiomyocyte tumor lineage was pre-treated with fentanyl and generated cell model of hypoxia-reoxygenation (H/R). Relative expression of MALAT1, miR-145, and Bnip3 mRNA in cells was determined by quantitative real-time PCR. Cardiomyocyte H/R injury was indicated by lactate dehydrogenase (LDH) release and cell apoptosis. The results showed that fentanyl abrogates expression of responsive gene for H/R and induces downregulation of MALAT1 and Bnip3 and upregulation of miR-145. We found that miR-145/Bnip3 pathway was negatively regulated by MALAT1 in H/R-HL-1 cell with or without fentanyl treatment. Moreover, both MALAT1 overexpression and miR-145 knockdown reverse cardioprotective effects of fentanyl, as indicated by increase in LDH release and cell apoptosis. The reversal effect of MALAT1 for fentanyl is confirmed in cardiac ischemia/reperfusion (I/R) mice. In summary, lncRNA-MALAT1 is sensitive to H/R injury and abrogates cardioprotective effects of Fentanyl by negatively regulating miR-145/Bnip3 pathway.

To investigate the effects of ligustrazine on acute lung injury induced by blunt chest trauma.This study was performed in the Animal Center of Renmin Hospital of Wuhan University, Wuhan, China between September 2009 and September 2010. Male Sprague-Dawley rats were randomly allocated into 4 groups: sham control group (group C, n=60), ligustrazine treatment group (group C+L, n=60), blunt chest trauma model group (group T, n=60), and the trauma plus ligustrazine treatment group (group T+L, n=60). The lung contusion was induced as previously described. Animals of the T+L group were intraperitoneally injected with ligustrazine. Acute lung injury was evaluated by histopathology of the lung, and apoptosis was determined by terminal dUTP nick-labeling. Pulmonary edema was estimated using Evans blue dye extravasation and wet/dry ratios of lung tissue. The expression of caspase-3, Bcl-2, and Bax in the lung, as well as blood plasma tumor necrosis factor (TNF)-alpha were also measured.The ligustrazine treatment significantly attenuated lung injury induced by blunt chest trauma, as shown by decreased apoptosis index, and pulmonary edema (p=0.04). The blood plasma TNF-alpha level after blunt chest trauma significantly deceased after the administration of ligustrazine (p=0.03). In addition, the ligustrazine treatment significantly alleviated the expression of caspase-3 (p=0.03), and increased the ratio of Bcl-2 to Bax (p0.03).Ligustrazine effectively protects lung injury induced by blunt chest trauma, and the protective effects seem to be mediated by attenuation of cell apoptosis via an increased ratio of Bcl-2/Bax and decreased caspase-3 activity.

To observe the influence of therapy with Chinese medicine Lirukang Granule (, LRKG) combined with psychological intervention on anxiety states and sex hormones in patients with cyclomastopathy and menoxenia.A total of 470 subjects were randomly assigned to three groups by the net-central randomization system, the treatment group (161 patients, treated with LRKG and psychological intervention), the Chinese medicine group (157 patients, treated with LRKG), and the psychological intervention group (152 patients, treated with psychological intervention). The dose of LRKG was 12 g three times per day; psychological intervention included establishing relations, cognitive intervention and psychological persuasion, 30-40 min per session, once a week. The therapy duration for all groups was three months. The efficacy was compared and anxiety state/State-Trait Anxiety Invertory (STAI) scoring was measured before and after treatment. The serum estradiol (E2), progesterone (P), prolactin (PRL) and follicle stimulating hormone (FSH) levels of 60 patients selected randomly from each group during the luteal phase were measured before and after treatment, and a group of 20 healthy women were evaluated for comparison. A follow-up was arranged for one year after treatment.Thirty subjects were lost to follow-up. (1) Comparison of efficacy: the markedly effective rate and the total effective rate of the treatment group were 86.67% (131/150) and 98.00% (147/150), respectively; of the Chinese medicine group, 64.58% (93/144) and 90.27% (130/144), respectively; and of the psychological intervention group, 0% (0/146) and 3.42% (5/146), respectively. The markedly effective rate and the total effective rate in the treatment group were significantly higher than those in the Chinese medicine and psychological intervention groups (P0.05). (2) Comparison of STAI scoring: STAI scoring was decreased dramatically in the treatment group after treatment compared with that of the Chinese medicine group (P0.01), but there was no significant difference compared with the psychological intervention group. (3) Comparison of levels of sex hormones: E2, P, PRL and FSH of the three patient groups were disordered before treatment, and significantly different from healthy women (P0.01). After treatment, the levels of P and FSH of the treatment group were significantly increased (P0.01), E2 and PRL were significantly reduced, which were also significantly decreased compared with the psychological intervention groups (P0.01). (4) FOLLOW-UP: the markedly effective rate and the total effective rate of the treatment group remained higher than those of the other two groups after one year of treatment (P0.05). (5) Adverse reactions: no obvious adverse reactions were found among the three groups.Therapy with Chinese medicine combined with psychological intervention was effective for short-term and long-term treatment of cyclomastopathy and menoxenia. The mechanism might be related to the regulation of sex hormones.

Vascular endothelial growth factor (VEGF) plays important roles in establishing collateral circulation of ischemic myocardium. This study aimed to investigate the effect of isoflurane on VEGF expression and the potential intracellular signal transduction pathway in cultured rat myocardial cells in order to further reveal the molecular mechanism of myocardial preservation of isoflurane.Primary myocardial cells of Sprague-Dawley rats were isolated and cultured. They were divided randomly into control group, isoflurane group, protein kinase C (PKC) inhibitor group and PKC inhibitor+isoflurane group where cells were respectively incubated without any treatment, treated by 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC) of isoflurane for 6 hours, by PKC inhibitor calphostin C at a final concentration of 50 nmol/L and by 50 nmol/L calphostin C+1.0 MAC isoflurane for 6 hours. VEGF expression was detected by enzyme-linked immunosorbent assay (ELISA) and the expression levels of PKC isoforms were determined by Western immunoblotting method.Isoflurane increased the VEGF expression in myocardial cells in a dose-dependent way. VEGF levels were significantly higher in 1.0 and 1.5 MAC isoflurane groups than in the control group (both P0.01). The effect of isoflurane on upregulating VEGF expression was blocked by PKC inhibitor calphostin C (P0.01), but calphostin C did not alter VEGF expression (P0.05). Isoflurane induced the activation and translocation of PKCε. Immunoblotting analysis revealed that the immunoreactivity of PKC ε increased significantly in the membrane fractions and deceased significantly in the kytoplasm fractions for cells treated with 1.0 MAC isoflurane as compared with the untreated cells, but not of PKC-α, PKC-δ and PKC-ζ (P less than 0.01).Isoflurane induces myocardial cells to release VEGF through activating PKC-epsilon from the endochylema to the cytomembrane, suggesting a possible novel mechanism of isoflurane protecting myocardial cells.

To investigate the effects of penehyclidine hydrochloride on apoptosis of lung tissue cells and its mechanism in acute lung injury following blunt chest trauma in rats.Sprague Dawley (SD) rats (n equal to 54) weighing (250+/-5) g were divided equally and randomly into three groups: normal control group (C group, n equal to 18), trauma model group (T group, n equal to 18) and penehyclidine hydrochloride treatment group (P group, n equal to 18). Each group was further divided into three subgroups according to the time points of 3, 12 and 24 hours after experiment (at each time point, n equal to 6 for each subgroup). Rats of P group were intraperitoneally injected with penehyclidine hydrochloride for 2 mg/kg immediately after blunt chest trauma and rats in its 24 hours subgroup were once again injected with penehyclidine hydrochloride in the same dose 12 hours after injury. Lung tissue samples were collected at every time point and cell apoptosis in lung tissues were measured by TUNEL. Apoptotic index (AI) was calculated, expressions of bax and bcl-2 were detected by immunohistochemical staining of SABC, and lung tissue sections were taken for light and electron microscopic observation.As compared with C group, at every time point, AI and expressions of bax and bcl-2 in T group were higher (P less than 0.05), and the ratio of bcl-2/bax markedly decreased (P less than 0.05), especially in the 24 hours subgroup. The ratio in T group (0.468+/-0.007) was lower than that in C group (1.382+/-0.058, t equal to 12.5, P less than 0.01). Lung tissue injuries were significant under a light microscope, and the number of apoptotic cells increased obviously under a transmission electron microscope. As compared with T group at the same phase, AI and expression of bax decreased in P group (P less than 0.05 and P less than 0.01), while the expression of bcl-2 increased significantly (P less than 0.01), and the ratio of bcl-2/bax markedly increased (P less than 0.05), especially in the 24 hours subgroup. The ratio in P group (1.012+/-0.070) was much higher than that in T group (0.468+/-0.007, t equal to 8.3, P less than 0.01). The injury of lung tissues was relieved, and apoptosis of cells decreased obviously under a transmission electron microscopic observation.Apoptosis and expressions of bax and bcl-2 in lung tissues might be involved in the pathogenesis of lung injury induced by blunt chest trauma. Penehyclidine hydrochloride can alleviate lung injuries by inhibiting apoptosis of lung tissue cells, during which effects of penehyclidine hydrochloride on regulating expressions of bax and bcl-2 may play an important role.

To investigate the effect of ischemic postconditioning (IPO) on acute lung ischemia-reperfusion (I/R) injury and the protein expression of haeme oxygenase-1 (HO-1), a cytoprotective defense against oxidative injury.After being anesthetized with chloralhy- drate, forty-eight healthy SD rats were randomly divided into 6 groups (8 in each): sham operation group (S group); I/R group: left lung hilum was clamped for 40 minutes followed by 105 minutes of reperfusion; IPO group: left lung hilum was clamped for 40 minutes and postconditioned by 3 cycles of 30 seconds of reperfusion and 30 seconds of reocclusion; Hemin (HM)+ I/R group: hemin, an inducer of HO-1 was injected intraperitoneally at 40 micromol/kg/day for two consecutive days prior to 40 minutes clamping of left lung hilum; ZnPPIX+IPO group: zinc protoporphyrin IX, an inhibitor of HO-1 was injected intraperitoneally at 20 mg/kg 24 hours prior to 40 minutes clamping of left lung hilum; and HM+S group: HM was administered as in the HM+I/R group without inducing lung I/R. Arterial partial pressure of oxygen (PaO(2)) and malondialdehyde (MDA) content in serum were assessed. The left lung was removed for determination of wet/dry lung weight ratio and expression of HO-1 protein by immuno-histochemical technique and for light microscopic examination.The PaO(2) was significantly lower in all the experimental groups compared with sham group (90 mm Hg +/- 1 mm Hg). However, the values of PaO(2) in IPO (81 mm Hg +/- mm Hg) and HM+I/R (80 mm Hg+/- mm Hg) were higher than that in I/R (63 mm Hg +/- 9 mm Hg) and ZnPPIX+IPO (65 mm Hg +/- 8 mm Hg) groups (P less than 0.01). The protein expression of HO-1 in lung tissue was significantly increased in I/R group compared with S group (P less than 0.01). While the HO-1 protein expression was higher in IPO and HM+I/R groups as compared with I/R group (P less than 0.05, P less than 0.01). The lung wet/dry (W/D) weight ratio and MDA content in serum were significantly increased in I/R group as compared with S or HM+S groups (P less than 0.01), accompanied by severe lung tissue histological damage, which was attenuated either by IPO or by HM pretreatment (P less than 0.01, IPO or HM+I/R vs. I/R). The protective effect of IPO was abolished by ZnPPIX.Ischemic postconditioning can attenuate the lung ischemia-reperfusion injury through upregulating the protein expression of HO-1 that leads to reduced post-ischemic oxidative damage.

We investigated whether transient systemic ischemia can precondition the heart against the ensuing ischemic insult. Rabbits were randomly divided into systemic ischemic preconditioning (SIP), hemodilution (HD) and control (C) groups. SIP was induced by rapidly withdrawing blood from femoral artery and maintaining the mean artery pressure at 50 mmHg for 10 min. Afterwards, 50% of the withdrawn blood was re-infused with equal volumes of 6% deferoxamine-conjugated hydroxyethyl-starch (D-HES). Hemodilution in HD group was achieved by withdrawing blood at 8 ml/kg accompanied by concomitant infusion of equal volumes of D-HES. Animals were subjected to 30 min of coronary artery occlusion followed by 120 min of reperfusion. Cardiac output (CO) (thermodilution method), plasma malondialdehyde and nitric oxide content were measured at baseline and until 120 (R120) min of reperfusion. At R120, CO in group-C was significantly lower than its baseline value, accompanied by a significant reduction in nitric oxide production and increase in malondialdehyde concentration; CO in group-SIP and group-HD maintained at baseline levels throughout reperfusion. At R120, CO in group-SIP, but not in group-HD, was significantly higher than that in group-C. It is concluded that transient SIP followed by hemodilution with D-HES facilitates early functional recovery of the ischemic-reperfused rabbit hearts.

To investigate the effect of Radix Paeoniae Rubra (RPR) on the expression of heme oxygenase (HO-1) and induced nitric oxide synthase (iNOS) in endotoxin-induced acute lung injury in rats and its protective mechanism.Forty Wistar rats were divided randomly into 5 groups with 8 rats in each group: saline control group (NS group), lipopolysaccharide group (LPS group), RPR-treatment group, RPR-prevention group and Hemin group. The effect of RPR on protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, malondialdehyde (MDA) content in the lung and the activity of serum NO were observed. Arterial blood was drawn for blood-gas analysis. The expression of HO-1 and iNOS in lung tissues was detected by immunohistochemistry and morphometry computer image analysis. The histological changes of the lung were observed under light microscope.Compared with that in NS group, the expression of HO-1 and iNOS was markedly increased in LPS group (P0.01). In RPR-treatment, RPR-prevention, and Hemin groups, the expression of iNOS was significantly lower, while the expression of HO-1 was higher than that in LPS group (P0.05). The protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, the content of MDA and the activity of serum NO in LPS group were significantly higher than those in NS group (P0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in the LPS group (P0.01); these parameters of lung injury however, were significantly lower in RPR-treatment, RPR-prevention, and Hemin groups than LPS group (P0.05 or P0.01). The pathologic changes of lung tissues were substantially attenuated in RPR-treatment, RPR-prevention, and Hemin groups than LPS group.The high expression of HO-1 reflects an important protective function of the body during lipopolysaccharide-induced acute lung injury. The protective effect of RPR on lipopolysaccharide-induced acute lung injury is related to the inhibition of iNOS expression and the induction of HO-1 expression.

We investigated whether propofol can inhibit tumor necrosis factor (TNF)-alpha-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs). Isolated HUVECs were cultured in Dulbecco's modified Eagle medium supplemented with 20% bovine calf serum. HUVECs in untreated and propofol control groups were cultured at 37 degrees C for 24.5 h. HUVECs in the TNF treatment groups were initially cultured for 30 min in the presence of TNF or various concentrations of propofol, respectively, which were then cultured for 24 h with the addition of TNF at 40 ng/mL in the medium. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and confirmed by electron microscopy. The antiapoptotic Bcl-2 and proapoptotic Bax protein expressions were measured by immunocytochemical analysis. TNF stimulation resulted in a reduced Bcl-2/Bax ratio and increased apoptotic index (AI: percentage of apoptotic cells) in HUVECs. Propofol, at concentrations/=12 muM, significantly (P0.001) and dose-dependently attenuated TNF-induced increase in AI and decrease in Bcl-2/Bax ratio. This was accompanied by increases in nitric oxide production. There is an inverse correlation between the ratio of Bcl-2/Bax expression and AI (P = 0.0009). These results suggest that propofol, at clinical relevant concentrations, can reduce TNF-induced HUVEC apoptosis.

To study the pharmacological effect of Shugan Yiyang(SGYY) capsule.kongming mice and Wistar rats were used to observe the effects of SGYY capsule on sexual desire, erection, ejaculation and fatigue. The weight of prostate, seminal vesicle, testes, levators and thymus and serum testosterone level were also measured. Furthermore, Rhesus monkey were used to construct animal model of erectile dysfunction. Effects of SGYY capsule on sexual behavior, penile blood flow and electromyogram were observed.SGYY capsule can remarkably reduce the incubation period of erection, ejaculation and innovate the sexual desire,erection, ejaculation both on rats and rhesus monkeys. The weight of prostate, seminal vesicle, testes, levators in mice and serum testosterone level of rats increased while the weight of thymus decreased. It can also diminish the luminar of vein and reduce the venous outflow while the transmission of peripheral nervous system remained stable.SGYY capsule can remarkably improve the erectile activity, sexual desire and ejaculatory activity. The mechanism of SGYY capsule may be related to the increase of androgen and adrenocorticohormone levels. as well as the reduction of penile venous outflow. [Key words] shuganyiyang capsule; er

To investigate the effect of Shenfu Injection (SF, ginesenoside and aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells during ischemia-reperfusion in rats and its potential mechanisms.Ischemia-reperfusion model was established in rats. Twenty-four rats were divided into 3 groups with 8 rats in each, eg, ischemia-reperfusion (I/R) group, SF-treated group, and control group. In both SF and I/R groups, the superior mesenteric artery was closed with forceps for 1 hour and then reperfused for 2 hours. Either SF (3 ml/kg, SF group) or normal saline (I/R and control groups) was injected intravenously and continuously for 5 ml/kg with a micropump before the superior mesenteric artery was closed. The superior mesenteric artery was not closed for animals in control group. The expression of casapse-3 and Fas, and the level of TNF-alpha and pathological changes of the ileal mucosal tissue were assayed.(1) The number of apoptosis cells increased obviously in I/R group and was significantly higher than that in SF and control groups (P0.05). (2) The expression of caspase-3, Fas, and TNF-alpha was significantly higher in I/R group than SF and control groups (P0.01); however, there was not significant difference in the expression of capase-3 between control group and SF group. There was a positive correlation between the expression of caspase-3, Fas, and TNF-alpha, and the number of apoptosis cells. (3) Under light microscope, intestinal mucosal impairment was found milder in SF group than I/R group (P0.05).SF can depress the apoptosis of intestinal mucosal epithelial cells during ischemia-reperfusion by restraining the expression of TNF-alpha, Fas, caspase-3, and accordingly alleviate the ischemia and reperfusion injury of intestinal mucosal epithelial cells.

To identify the protective effects of hypovolemic hypotension preconditioning on cardiopulmonary function after myocardial ischemia/reperfusion injury and to explore the possible mechanism.Twenty-four male white rabbits were randomly assigned to two groups. In the control group, ischemia/reperfusion animals(Group I/R, n=10) were subjected to thirty-minute occlusion of left anterior descending coronary artery and two-hour reperfusion. Animals in hypovolemic hypotension preconditioning group (Group HHP, n=14) experienced brief systemic ischemia preconditioning through blood withdrawal to lower blood pressure to 40%-50% of the baseline before myocardial ischemia/reperfusion. Hemodynamic parameters were recorded. Blood sample was taken to measure superoxide dismutase (SOD), malondialdehyde (MDA) and nitrogen monoxide (NO) changes with blood gas analysis. Myocardium specimens were sampled to examine apoptosis-related gene interleukin-1 beta converting enzyme (ICE) mRNA.Cardiac mechanical function and lung gas exchange remained stable in Group HHP with a significant increase in NO level; while in Group I/R without preconditioning, cardiopulmonary dysfunction was present after 2 h reperfusion associated with a significant reduction in NO formation and an increase in MDA (P0.001). There was negative expression of ICE mRNA in the two groups.Hypovolemic hypotension preconditioning significantly improves cardiopulmonary function and increases NO formation and the protective benefit associated with hypovolemic hypotension preconditioning of the heart may be regulated through NO mediated mechanism.

To study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved.Twelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly.Infusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P0.01 and P0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P0.05).MP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.

To investigate the effect of Shen-Fu (SF) injection on gastrointestinal tract injury and its potential mechanism.Thirty-eight patients undergoing elective open heart surgery were assigned to Group C (control group, n=18) and Group SF (n=20) randomly. In Group SF, the patients received intravenous injection of SF (0.5 ml/kg) at the beginning of the surgery followed by a continuous infusion of 100 ml SF (1.0 ml/kg) solution diluted by saline at a rate of 0.004 ml x Kg(-1) x min(-1) with a Grasby pump. The control group was injected with normal saline in the same volume. Gastric intramucosal pH (pHi), activity of blood diamine oxidase (DAO), and concentrations of blood LPS and IL-6 were measured before CPB (S0) and 1 h (S1) and 2 h (S2) after aortic declamping, respectively.In Group C, pHi value was significantly lower at S1 and S2 than at S0 (mean P0.01) and blood DAO and concentrations of LPS and IL-6 were significantly higher at S1 and S2 than at S0 (mean P0.01). In Group SF, pHi was obviously lower at S1 and S2 than at S0 (P0.05) but LPS and IL-6 levels and DAO were higher at S0 (mean P0.05). Blood DAO and LPS level demonstrated significant negative correlations with pHi (mean P0.01) while LPS concentration showed a positive correlation with blood DAO (P0.01) and IL-6 concentration (P0.05). At S1 and S2 after aortic declamping, the levels of pHi were higher in Group SF than in Group C (mean P0.01 ) but DAO and LPS and IL-6 levels were significantly lower in Group SF than in Group C (P0.01).SF has a protective effect on gastrointestinal tract and can reduce inflammatory actions.

INTRODUCTION: Tumor necrosis factor-alpha (TNF) is increased in pathological conditions such as myocardial ischemia-reperfusion and in diabetes, exacerbating cardiovascular complications. Nitric oxide (NO) may play a dual role in TNF-induced vascular endothelial cell apoptosis, 1;2 a phenomenon accompanied by increased oxidative stress. We investigated whether the concomitant application of propofol (P), an intravenous anesthetic with antioxidant properties, with NO donor L-arginine (LA) could confer protective effects on TNF induced human umbilical vein endothelial cells (HUVECs) apoptosis.