甲氰咪呱对非酒精性脂肪性肝炎(NASH)大鼠肝微粒体细胞色素P450的影响

目的研究甲氰咪呱对非酒精性脂肪性肝炎（NASH）大鼠肝微粒体细胞色素P450的影响。方法通过高脂饮食制作非酒精性指肪性肝炎（NASH）动物模型，给予甲氰咪呱灌胃治疗，观察肝组织病理形态变化，进行炎症活动计分，同时测定细胞色素P450（CYP450）和细胞色素2E1（CYP2EI）含量及ALT、AST，并与对照组比较。结果与正常组比较，模型组大鼠ALT、AST及CYP450和CYP2EI含量明显升高；与模型组比较，甲氰咪呱治疗组CYP450和CYP2EI含量均明显下降，（P〈0．05），ALT、AST及炎症活动计分明显低于模型组（P〈0．05）。结论甲氰咪呱能显著改善NASH大鼠肝脏功能及形态损伤，可能通过抑制肝细胞微粒体CYP450和同功酶CYP2EI的表达发挥作用。

Effects of cimetidine on the expression of hepatocyte cytochrome P450 in rats with nonalcoholic steatohepatitis (NASH)

Objectives To study the effects of cimetidine on the expression of hepatocyte cytochrome P450 in rats with nonalcoholic steatohepatitis (NASH). Methods Nonalcoholic steatohepatitis(NASH) animal models were setup by high fat diet. All rats were randomly divided into control group,model group and treatment group. NASH treatment groups were intragastrically treated with cimetidine(200 mg/d)12 week.The pathological change of liver tissue were observed under light microscope.The levels of cytochrome P450(CYP450), CYP2E1 and the changes of alanine aminotransferase(ALT),aspartate aminotransferase(AST) were measured and compared with those in the control groups. Results Comparing with control groups,the serum levels of ALT,AST and the tissue contents of CYP450 and CYP2E1 in model groups were elevated(P<0.05).However,after cimetidine treatment,the contents of CYP450 and CYP2E1,and levels of ALT,AST as well as the histological activity index were decreased significantly (P<0.05). Conclusions Cimetidine can improve the function of liver of NASH rats. It may play the role by means of inhibition of hepatocyte cytochrome CYP450 and CYP2E1 expression.