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Objective: To examine the protective effects of inhibition of c-jun N-terminal kinase (JNK) stress signal pathway on the injured barrier in endotoxemic rats., Methods: Twenty-four male Sprague Dwaley (SD) rats were randomly divided into control group, endotoxemia model group and JNK inhibitor group (n=8 each) to receive administration of: 1 normal saline 2 ml/kg + PPCES 2.5 ml/kg [vehicle of JNK inhibitor (SP600125), control group]; 2 lipopolysaccharide (LPS) 10 mg/kg + PPCES 2.5 ml/kg (endotoxemia model group); 3 LPS 10 mg/kg + JNK inhibitor (SP600125) 10 mg/kg (JNK inhibitor group). The activity and survival rate of the rats were recorded. Ileum tissue samples were collected 12 hours after drug administration for pathological examination. Blood samples were collected at the same time for determination of concentration of D-lactate by enzyme linked immunosorbent assay (ELISA)., Results: Rats in control group were active normally, and there was no death. Pathological examination showed there was edema of ileal mucosa, and shortening of villus and inflammatory cell infiltration in model group as compared with control group. JNK inhibitor greatly ameliorated the lesions compared with model group. The concentration of D-lactate (µg/L) in model group was significantly higher than that in control group. (943.8 ± 439.6 vs 227.9 ± 130.0, P<.05). JNK inhibitor could decrease the plasma D-lactate concentration (637.4 ± 114.4 vs 943.8 ± 439.6, P<.05)., Conclusion: Inhibition of the JNK stress signal pathway could attenuate the intestinal barrier injury in endotoxemic rats.

Objective: To observe the effects of low-level laser irradiation on mesenteric microcirculation of rats in vivo in the early stage of endotoxemia (ETM)., Methods: The experimental model of ETM was reproduced by injection of lipopolysaccharide (LPS). Sixty healthy male Sprague-Dawley (SD) rats were divided into three groups used random number table: control group, LPS group and low-level laser irradiation group, each group included 20 rats which were subdivided into four temporal subgroups (1, 2, 4, 6 hours, respectively). In low-level laser irradiation group, the rats were irradiated by type SLT semiconductor laser (650 nm, 5 mW) on unilateral femoral artery and vein, and blood vessel of the ear concurrently for 30 minutes. The interference course was vertical irradiation taken at 30 minutes after the injection of LPS. At 1, 2, 4, 6 hours after the injection of LPS, changes in mesenteric microcirculation and microcirculatory blood flow were recorded with the laser Doppler flowmeter, the velocity of red blood cells in venules was observed, and the number of open capillaries and adherent leukocytes were recorded., Results: The blood flow velocity (mm/s) of the mesenteric microcirculation in LPS group was accelerated at 1 hour and 2 hours after LPS injection (1 hour: 0.190+/-0.007 vs. 0.174+/-0.009, 2 hours: 0.200+/-0.010 vs. 0.172+/-0.015, both P<0.05, respectively), but decelerated at 6 hours (0.116+/-0.015 vs. 0.164+/-0.011, P<0.05). The blood flow volume in the mesenteric vessels and the number of open capillaries did not show any significant change at that time. Significant increase in number of adherent leukocytes was observed at 2, 4, 6 hours after injury (2 hours: 2.60+/-1.14 vs. 0.40+/-0.55, 4 hours: 5.40+/-0.89 vs. 0.40+/-0.55, 6 hours : 5.40+/-1.52 vs. 0.60+/-0.90, all P<0.05, respectively). The state of blood flow in the microcirculation became abnormal. After irradiated with laser in low dose, the blood flow velocity was smooth and stable (mm/s, 1 hour: 0.174+/-0.011, 2 hours: 0.180+/-0.023, 4 hours: 0.168+/-0.013, 6 hours: 0.162+/-0.023), and the number of adherent leukocytes was reduced significantly at 4 hours and 6 hours than that in LPS group (4 hours: 2.00+/-0.71 vs. 5.40+/-0.89, 6 hours: 2.60+/-1.52 vs. 5.40+/-1.52, both P<0.05) and the microcirculatory flow state was improved obviously., Conclusion: Low-level laser irradiation may ameliorate the local mesenteric microcirculation, alleviate the microcirculatory disorder in early stage of ETM.

Objective: To compare the effects of posttreatment with isoflurane versus propofol on pulmonary alveolar capillary barrier (PACB) in endotoxemic rats., Methods: Ninety-six male Sprague-Dawley rats weighing 250 to 350 g were randomly divided into 6 equal groups to be administered with intravenous lipopolysaccharide (LPS, 4 mg/kg) or equivalent volume of normal saline (NS) and treated with intravenous pentobarbital (C, 20 mg x kg(-1) x h(-1)), inhaled isoflurane (I, 0.55%) or intravenous propofol (P, 10 mg/kg bolus, 40 mg x kg(-1) x h(-1)) 2 hours after the establishment of endotoxemic model: NS-C, NS-I, NS-P, LPS-C, LPS-I, and LPS-P groups. The rats were ventilated for 2 h. The mean arterial pressure (MAP) and arterial blood gas were assessed hourly for 4 h. One cohort (n = 8 per group) was subjected to bronchial alveolar lavage in the left lungs for determination of protein concentration in the bronchial alveolar lavage fluid (BALF) and the lung permeability index (LPI, BALF protein concentration/serum protein concentration). Then the right lungs were removed to undergo light and electron microscopy and measurement of the wet wet-to-dry weight ratio (WW/WD). In a second cohort (n = 8 per group), Evans blue dye (EBD, 30 mg/kg) was injected 30 min before the end of the experiment to determine the EBD content in the lung., Results: The MAP, pH, PaCO(2), and PaO(2) were not different significantly within the three NS groups and the three LPS groups and WW/WD did not show any difference among all six groups. The LPI and EBD content in lung were significantly higher in the LPS-C group [8.1 x 10(-3) +/- 2.4 x 10(-3) and 0.628 +/- 0.082 absorption unit (AU) respectively] than in NS-C group (3.3 x 10(-3) +/- 2.2 x 10(-3) and 0.479 +/- 0.154 AU respectively, both P < 0.05), and were higher in the LPS-P group (9.1 x 10(-3) +/- 2.2 x 10(-3) and 0.664 +/- 0.028 AU respectively) than in the LPS-I group (5.5 x 10(-3) +/- 2.0 x 10(-3) and 0.517 +/- 0.048 AU respectively, both P < 0.05). Light microscopy showed more severe lung injury changes in the LPS groups than in the NS groups, especially in the LPS-P group. Electron microscopy found that the tight junctions between the adjacent pulmonary microvascular endothelial cells in the LPS-P groups were disrupted., Conclusion: Compared with posttreatment with propofol, posttreatment with isoflurane protects the PACB function and decreases the pulmonary permeability in endotoxemic rats.

The purpose of the present study was to investigate the effect of melatonin (MT) on the abnormal reactivity of thoracic aorta and pulmonary artery induced by lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into four groups randomly: (1) Vehicle group; (2) LPS group: LPS (4 mg/kg, i.p.); (3) LPS+MT group: MT (5 mg/ml, i.p.) was given 30 min before LPS and 60 min after LPS (4 mg/kg ,i.p); (4) MT group: received two doses of MT, 90 min after the first injection of MT another dose of MT was given. Six hours after LPS injection,the rats were killed and both thoracic aortic rings (TARs) and pulmonary artery rings (PARs)were prepared. The reactivity of TARs and PARs in the four subgroups was tested separately. The contraction response to phenylephrine (PE) and the endothelium-dependent relaxation response (EDRR) to ACh were observed with the isolated artery ring technique. Concentration-response curves were generated with ACh or PE (1 x 10(-8) - 1 x 10(-5) mol/L). Superoxide dismutes (SOD) activity and the content of malondialhyde (MDA) in artery tissues were detected. For TARs, LPS significantly reduced the contraction response to PE compared with the vehicle group (P<0.01) and the curve of cumulative dose responses to PE in the LPS group shifted downward. Although EDRR to ACh in the LPS group had the tendency to decrease but still showed no significant difference compared with the vehicle group (P>0.05). For PARs, EDRR to ACh was depressed significantly in the LPS group (P<0.01), while no effect on contraction response to PE in the LPS group was observed, compared with the vehicle group (P> 0.05). Compared with the LPS group, TARs in the LPS+MT group exhibited an increased contraction response to PE, but were still lower than that in the vehicle group. Similarly, EDRR to ACh of PARs in the LPS+MT group was improved significantly and there was no difference between the LPS+MT group and the vehicle group. The vascular reactivity was unaffected in MT group compared with the vehicle group in both TARs and PARs. SOD activity in the LPS +MT group increased significantly and the content of MDA decreased markedly compared with the LPS group. These results suggest that MT may improve the vascular reactivity in endotoxemia rats due to its antioxidant properties.

Aim: To investigate the effects of atrial natriuretic peptide(ANP) on constriction and relaxation of pulmonary artery and aorta in endotoxemia rat in vitro., Methods: 24 male SD rats were randomly divided into 3 groups, control group, LPS group, ANP therapy group. These groups were injected physiologic salt water, lipopolysaccharide (LPS 2 mg/kg) and LPS + ANP(LPS 2 mg/kg, ANP 2 microg/kg) into vein respectively. After 4 hours, rats were exsanguinated to kill and aorta and pulmonary artery were separated from heart-lung for experiment of blood vessel rings. Constriction effects of aorta and pulmonary artery by norepinephrine (NE), relaxation of aorta and pulmonary artery by acetylcholine (ACh) and sodium nitroprusside SNP) observed by perfusion system in vitro., Results: Sensitiveness of NE-induced (10(-9)-10(-7) mol/L) constriction of aorta in LPS group was attenuated and EC50 was increased, but its strength (3 x 10(-7)-10(-6) mol/L) was greater comparing with control group (P < 0.01). In ANP group, the NE-induced contractility of aorta was similar to LPS group (P > 0.05). Comparing with control group, NE-induced constriction of pulmonary artery exposure to LPS was reinforced especially in 3 x 10(-7)-10(-6) mol/L of NE (P < 0.01), but its EC50 was obviously higher (P <0.05). There was no significant difference between ANP group and control group in constriction of pulmonary artery (P > 0.05). Relaxation and sensitiveness of aorta and pulmonary artery exposure to LPS were evidently improved in ANP therapy group induced by ACh and SNP respectively (P < 0.01, P < 0.05) and their EC50 markedly decreased comparing with LPS group (P < 0.01, P < 0.05) respectively., Conclusion: ANP can suppress the reinforcing of NE-induced constriction of pulmonary artery exposure to LPS and partly or entirely reverse the attenuated relaxation of pulmonary artery and aorta induced by ACh and SNP in endotoxemia rats.