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Patients with acute myocardial infarction complicated with diabetes are more likely to develop myocardial ischemia/reperfusion (I/R) injury (MI/RI) during reperfusion therapy. Both HMGB1 and RAGE play important roles in MI/RI. However, the specific mechanisms of HMGB1 associated with RAGE are not fully clarified in diabetic MI/RI. This study aimed to investigate whether the HMGB1-RAGE axis induces diabetic MI/RI via regulating autophagy and apoptosis. A db/db mouse model of MI/RI was established, where anti-HMGB1 antibody and RAGE inhibitor (FPS-ZM1) were respectively injected after 10 min of reperfusion. The results showed that treatment with anti-HMGB1 significantly reduced the infarct size, serum LDH, and CK-MB level. Similar situations also occurred in mice administrated with FPS-ZM1, though the HMGB1 level was unchanged. Then, we found that treatment with anti-HMGB1 or FPS-ZM1 performed the same effects in suppressing the autophagy and apoptosis, as reflected by the results of lower LAMP2 and LC3B levels, increased Bcl-2 level, reduced BAX and caspase-3 levels. Moreover, the Pink1/Parkin levels were also inhibited at the same time. Collectively, this study indicates that the HMGB1-RAGE axis aggravated diabetic MI/RI via apoptosis and Pink1/Parkin mediated autophagy pathways, and inhibition of HMGB1 or RAGE contributes to alleviating those adverse situations. [ABSTRACT FROM AUTHOR]

Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P < 0.05, IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

Objective: To explore the effects of cromolyn sodium (CS) on intestinal ischemia-reperfusion (IIR) and its relationship with mast cell activation and protease-activated receptor 2 (PAR-2) expression., Methods: A total of 32 SD rats were randomly divided into 4 groups: sham-operated (S), intestinal ischemia reperfusion (IIR), CS (a mast cell stabilizer, CS, 25 mg/kg) and compound 48/80 (a mast cell degranulation, CP, 0.75 mg/kg) (n = 8 each). IIR was induced by clamping superior mesenteric artery for 75 min followed by reperfusion for 3 hours. The above agents were intravenously administrated at 5 min pre-reperfusion. Rats were then sacrificed and intestinal issues harvested for histological examinations. The tryptase expression and mast cell count were analyzed by immunohistochemistry. PAR-2 was analyzed by Western blot., Results: The Chiu's score (0.75 ± 0.21), mast cell count (10 ± 3), tryptase expression (125 ± 15) and PAR-2 expression (109 ± 10) of group S were the least while those of group CP the most (all P < 0.05). The Chiu's score (2.14 ± 0.64), mast cell count (15 ± 4), tryptase expression (138 ± 17) and PAR-2 expression (124 ± 12) of group CS were less than those of groups IIR and CP (all P < 0.05)., Conclusion: Cromolyn sodium may reduce IIR injury by stabilizing mast cell membrane and inhibiting the expressions of tryptase and PAR-2.

Objective: To observe the changes in systemic hemodynamics and their relations to the concentrations of nitric oxide, endothelin, prostacyclin, and thromboxane A2 after portal cavity clamping and opening in portal hypertensive canines., Methods: Twelve canines were randomly divided into control group and model group, and partial ligation of the portal vein was performed in the model group. Portal cavity clamping and opening was performed 12 weeks later in the two groups. The hemodynamic parameters including cardiac output index (CI), heart rate (HR), mean artery blood pressure (MABP), central venous pressure (CVP), pulmonary arteriole wedge pressure (PAWP), and systemic vascular resistance index (SVRI) were measured during the operation. Samples were obtained from the central vein at 3 time points during the operation for measuring NO, ET, PGI2, and TXA2., Results: Portal vein ligation and portal cavity clamping produced obvious changes in the systemic circulation of the dogs, and the alteration was milder in the control group. After obstruction of the portal vein, the NO levels in systemic circulation in portal hypertensive dogs declined obviously, but gradually recovered the normal level after reperfusion., Conclusion: Systemic circulation undergoes significant alterations after portal vein obstruction, but its changes in portal hypertensive dogs are milder than those in the control group, the mechanism of which needs further investigation.

Objective: To observe the changes in mixed venous oxygen saturation(SvO(2))during perioperative periods of orthotopic liver transplantation (OLT), and explore its clinical significances., Methods: Twenty patients in terminal stage of hepatic cirrhosis were scheduled for OLT under combined general anesthesia. Vigilance monitor (Edwards, USA) was employed to monitor perioperative SvO(2), oxygen delivery (DO(2)), oxygen consumption(VO(2)), oxygen extraction rate (ERO(2)) and body temperature, cardiac output (CO), and mean arterial blood pressure (MAP)., Results: Compared with the preoperative stage, SvO(2) elevated during 15 minutes of anhepatic stage (P<0.05), but decreased significantly during 30 minutes compared to that during 15 minutes of anhepatic stage. Then it was elevated significantly at 30 minutes after the reperfusion of the graft and at the end of operation (all P<0.05). Both DO(2) and VO(2) were decreased significantly during the anhepatic phase (both P<0.05), and increased significantly after graft reperfusion (all P<0.05); ERO(2) increased significantly after graft reperfusion (P<0.05). The level of SvO(2) was correlated with VO(2) significantly at each stage (all P<0.05), but not with DO(2) and hemoglobin (all P<0.05). SvO(2) was correlated well with CO before operation (P<0.05), but not at the other time points (all P>0.05)., Conclusion: Monitoring SvO(2) continually is of clinical significance in patients during OLT.