β-榄香烯对CLP诱导的脓毒症大鼠肝损伤的保护作用

Protective effect ofβ-elemene on liver injury of CLP-induced sepsis rats

目的:探讨β-榄香烯在盲肠结扎穿孔(CLP)诱导的脓毒症大鼠肝功能和炎症损伤中的保护作用。方法:50只Wistar大鼠分为健康对照组、模型组、模型+β-榄香烯25 mg/kg组、模型+β-榄香烯50 mg/kg组、模型+β-榄香烯100 mg/kg组。ELISA测定各组大鼠血清中天冬氨酸氨基转移酶(AST)、谷氨酸氨基转移酶(ALT)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、三酰甘油(TG)水平;HE染色观察肝脏病理损伤;Western blot检测肝组织中cleaved cas9、cleaved cas3蛋白表达水平,ELISA检测血清和肝组织中iNOS和IL-10含量,Western blot和免疫组化检测NF-κB P65蛋白表达水平。结果:与健康对照组相比,模型组大鼠血清中AST、ALT、LDL、TG水平升高,HDL水平降低(P<0.05),肝脏病理损伤严重,cleaved cas9、cleaved cas3蛋白表达水平升高,血清和肝组织中iNOS和IL-10含量增多,p-P65/P65水平升高(P<0.05)。与模型组相比,25 mg/kgβ-榄香烯给药治疗后,脓毒症大鼠血清和肝组织中各项指标均无明显差异,50 mg/kg和100 mg/kgβ-榄香烯给药治疗后,脓毒症大鼠血清中AST、ALT、LDL、TG水平明显降低,HDL水平升高(P<0.05),肝脏组织病理损伤得到明显改善,cleaved cas9、cleaved cas3蛋白表达水平明显降低(P<0.05),血清和肝组织中iNOS和IL-10含量明显减少(P<0.05),p-P65/P65表达水平显著下调(P<0.05)。结论:β-榄香烯对CLP诱导的脓毒症大鼠肝损伤具有保护作用,其机制可能与下调NF-κB P65蛋白表达有关。

Objective:To investigate the protective effect ofβ-elemene on liver function and inflammatory injury in rats with sepsis induced by cecal ligation and puncture(CLP).Methods:Fifty Wistar rats were divided into healthy control group,model group,model+β-elemene 25 mg/kg group,model+β-elemene 50 mg/kg group and model+β-elemene 100 mg/kg group.ELISA was used to detect aspartate aminotransferase(AST),glutamate aminotransferase(ALT),high-density lipoprotein(HDL),low-density lipoprotein(LDL)and triglyceride(TG)levels in serum of rats in each group;HE staining was used to observe liver pathological damage;expression levels of cleaved cas9 and cleaved cas3 pathway related proteins were detected by Western blot,and ELISA was used to detect concentrations of iNOS and IL-10 in serum and liver tissue.Western blot and immunohistochemical were used to detect NF-κB P65 protein expression level.Results:Compared with healthy control group,serum levels of AST,ALT,LDL and TG in model group were increased,while HDL level was decreased(P<0.05).Liver pathological damage was severe,protein expression levels of cleaved cas9 and cleaved cas3 were increased.Levels of iNOS and IL-10 in serum and liver tissue were increased,and p-P65/P65 was increased(P<0.05).Compared with model group,after 25 mg/kgβ-elemene was administered,there were no significant differences in serum and liver tissue indexes of septic rats.50 mg/kg and 100 mg/kgβ-elemene after drug treatment,serum levels of AST,ALT,LDL and TG in sepsis rats were significantly decreased,while HDL level was increased(P<0.05),liver tissue pathological damage was significantly improved,expressions of cleaved cas9 and cleaved cas3 protein were significantly decreased(P<0.05),levels of iNOS and IL-10 in serum and liver tissue were significantly decreased(P<0.05),and expression level of p-P65/P65 was significantly decreased(P<0.05).Conclusion:β-elemene has a protective effect on liver damage in CLP-induced sepsis rats,the mechanism of action may be related to down-regulation of NF-κB P65 protein expression.