二甲双胍对非酒精性脂肪肝大鼠肝细胞CYP2E1表达的影响

Effects of Metformin on CYP2E1 Expression of Liver in Rats with Nonalcoholic Fatty Livers Disease

目的探讨细胞色素P4502E1(CYP2E1)在非酒精性脂肪肝形成中的作用及二甲双胍对非酒精性脂肪肝的治疗作用。方法 24只雄性Wistar大鼠分为3组,每组8只。对照组用普通饲料喂养,高脂组用脂肪乳灌胃,二甲双胍组在脂肪乳灌胃的同时给予二甲双胍灌胃。喂养8周后处死大鼠,测量体重、肝脏指数、ALT、AST、HDL-C、TG、空腹血糖(Fbg),空腹胰岛素(Ins)。大鼠肝脏组织进行HE染色观察脂肪变及炎症坏死程度。用高胰岛素正葡萄糖钳夹实验评估大鼠胰岛素敏感度。用免疫组织化学染色和反转录聚合酶链反应(RT-PCR)观察CYP2E1的表达。结果二甲双胍组大鼠ALT、AST、TG明显低于对照组和髙脂组。二甲双胍组的肝脏脂肪变程度轻于高脂组。二甲双胍组大鼠的葡萄糖输注率高于对照组。二甲双胍组大鼠的肝脏CYP2E1表达低于高脂组。结论二甲双胍能有效地治疗非酒精性脂肪肝,可能与抑制CYP2E1的表达有关。

Objective To study the cytochrome P450 2El （ CYP2E1 ） in the role of non - alcoholic fatty liver and observe the thera- peutic effect of metformin on non - alcoholic fatty liver. Methods Twenty four male wistar rats were randomly divided into control group, high fat group and metformin group （ n = 8 ）. Mice in control group were fed with normal diet. Mice in High - fat and metformin group were fed with fat emulsion by intragastrie administration. Mice in The metformin group were given metformin at the same time. Eight weeks later, hyperinsulinemic - euglycemie clamp test were performed to evaluate insulin sensitivity. Blood samples were taken to measure the ALT, AST, HDL- C, TG, fasting glucose （Fbg） and fasting insulin （Ins）. CYP2E1 expression in hepatic tissue was detected by immunohistochemieal stain and reverse transeriptase polymerase chain reaction （RT - PC R）. Results The level of serum ALT, AST, and TG in metformin group mice was significantly higher than that in control and high fat mice. The degree of liver steatosis in metformin group mice was significantly lighter than that in the high - fat group mice and the glucose infusion rate was also significantly higher than that in the high - fat group mice. Compared with the high - fat group mice, the expression of CYP2E1 in liver decreased markedly in met-formin group mice. Conclusion The data indicate that metformin treatment of nonalcoholic fatty liver is effective and this may be resuh of inhibition of the CYP2E1 expression.