西咪替丁和水飞蓟宾对非酒精性脂肪性肝炎大鼠细胞色素P450的作用

Effects of cimetidine and silybin on cytochrome P450 in rats with nonalcoholic steatohepatitis

目的:研究西咪替丁、水飞蓟宾对大鼠肝微粒体细胞色素P450(CYP450)表达的影响。方法:应用高脂饲料诱导的NASH大鼠模型,给予西咪替丁及水飞蓟宾灌胃,紫外分光光度计测量CYP450及同工酶CYP2E1含量,RT-PCR法检测TIMP-1、TIMP-2,生化分析仪测定转氨酶等指标。结果:与模型组比较,西咪替丁组大鼠的CYP450、CYP2E1、TIMP-1、TIMP-2含量均下降,ALT、AST水平也下降;水飞蓟宾对CYP450、CYP2E1无影响,但能使TIMP-1、TIMP-2、ALT、AST含量下降。结论:西咪替丁、水飞蓟宾均能改善NASH大鼠肝功水平,西咪替丁通过抑制CYP450起作用,水飞蓟宾对CYP450无作用。

Objective： To study the effects of cimetidine and silybin on cytochrome P450 in rats with nonalcoholic steatohepatitis （NASH）. Methods：The rats were fed with high fatty food and the NASH model of rat were established. These animals were given cimetidine or silybin for 12 weeks. Then they were killed and their livers were collected. The contents of cytochrome（CYP） P450 and CYP 2E1 in the livers were examined by RT - PCR, and the level of the was determined by biochemical analyzer. Results： Compared with the NASH model group, the levels of CYP 450, CYP 2E1, TIMP - 1, TIMP - 2, ALT and AST decreased in cimetidine group, but the levels of TIMP - 1, TIMP - 2, ALT and AST decreased and the levels of CYP 450 and CYP 2El did not changed significantly. Conclusion： Both cimetidine and silybin can improve the functions of liver of NASH rats. Cimetidine plays the role by means of inhibition of expression CYP 450, but silybin has not significant effects on CYP 450.