蜡样芽孢杆菌对胆汁淤积大鼠的肝损伤和肠黏膜通透性的影响

Effect of Bacillus cereus on liver injury and intestinal mucosal permeability in rats with intrahepatic cholestasis

目的探讨蜡样芽孢杆菌(Bc)对肝内胆汁淤积大鼠的肝损伤和肠黏膜通透性的影响。方法将40只大鼠分为对照组、模型组及Bc低、高剂量组,每组10只。除对照组外,其余大鼠均单次灌胃α-荼基异硫氰酸盐(ANIT)建立胆汁淤积模型。Bc低、高剂量组于造模次日开始灌胃Bc(1.0×108、2.0×108 CFU/kg),对照组和模型组灌胃等体积蒸馏水,每天1次,连续5d。检测各组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、二胺氧化酶(DAO)、总胆红素(T-BIL)和乳酸(LA)的水平;观察各组大鼠肝组织病理学变化,免疫组织化学分析各组大鼠小肠组织中紧密连接蛋白Occludin和ZO-1的表达。结果与对照组比较,模型组大鼠血清中ALT、AST、DAO、T-BIL及LA水平明显升高,小肠组织中Occludin和ZO-1表达明显减少(P<0.05)。与模型组比较,Bc低、高剂量组大鼠血清中AST、DAO和LA等水平明显降低(P<0.05);肝组织病理学明显改善,小肠组织中Occludin和ZO-1的蛋白表达增加(P<0.05)。结论 Bc对胆汁淤积大鼠肝损伤有一定保护作用,可改善其肠黏膜通透性,其机制可能与上调小肠组织中紧密连接蛋白的表达有关。

Objective To investigate the effect of Bacillus cereus(Bc)on liver injury and intestinal mucosal permeability in rats with intrahepatic cholestasis.Methods Forty rats were divided into the control group,with the model group,and the Bc low-and high-dose groups,with 10 rats in each group.Animal models of intrahepatic cholestasis were induced by alpha-naphthylisothiocyanate(ANIT)excluding the normal control group.The Bc low-and high-dose groups were intragastrically administered Bc(1.0×10 8,2.0×10 8 CFU/kg)on the next day of modeling,and the control group and the model group were given an equal volume of distilled water once a day for 5 days.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),diamine oxidase(DAO),total bilirubin(T-BIL)and lactic acid(LA)of each group were detected.The pathological changes of liver tissues were observed,the expression of Occludin and ZO-1 proteins in the small intestine was analyzed by immunohistochemistry.Results Compared with the control group,the levels of ALT,AST,T-BIL,DAO and LA in the model group significantly increased,the expression of Occludin and ZO-1 in small intestine significantly decreased(P<0.05).Compared with the model group,the levels of AST,DAO and LA decreased(P<0.05);the liver pathologic changes were improved,the expression of Occludin and ZO-1 increased significantly(P<0.05).Conclusion Bc can protect the liver function and improve the intestinal mucosal permeability in rats with intrahepatic cholestasis,the mechanism may be related to the upregulation of tight junction protein expression in small intestine tissue.