降脂利肝颗粒对大鼠非酒精性脂肪肝模型CYP2E1基因和蛋白表达的影响

Effect of Jiangzhiligan Granules on CYP2E1 Gene and Protein Expression of Rat Model with Non-alcoholic Fatty Liver Disease

目的评价降脂利肝颗粒对大鼠非酒精性脂肪肝(NAFLD)模型细胞色素P4502E1(CYP2E1)基因和蛋白表达的影响,探讨该药的作用机制。方法选取20只健康SDF级Wistar大鼠,建立NAFLD模型,并按照随机数字表法分为预防组、模型组,每组各10只。自造模第2周起;给予预防组大鼠降脂利肝颗粒灌胃,每日1次,每次6 g·kg-1;给予模型组大鼠等量生理盐水灌胃;持续6周。比较两组大鼠肝脏组织病理学、肝功能、血脂、氧化指标及CYP2E1 m RNA和蛋白水平表达差异,总结降脂利肝颗粒对大鼠NAFLD模型CYP2E1基因和蛋白表达影响。结果预防组大鼠肝湿重、肝指数均低于模型组,差异有统计学意义(P<0.05),两组大鼠体质量比较,差异无统计学意义(P>0.05)。模型组大鼠肝细胞可见严重脂肪变性,变性范围占全部肝脏的50%~100%,预防组大鼠肝细胞可见部分脂肪变性,其脂肪变性程度低于模型组,差异有统计学意义(P<0.05)。预防组实验结束前AST、ALT、TC、TG、HDL-C、LDL-C、MDA均较造模2周后降低,SOD、GSH-PX、GSH均较造模2周后升高,差异有统计学意义(P<0.05)。实验结束前,预防组肝组织CYP2E1 m RNA、蛋白表达均低于模型组,差异有统计学意义(P<0.05)。结论降脂利肝颗粒对NAFLD模型大鼠CYP2E1基因和蛋白的表达具有下调作用,且表现出改善肝功能、血脂、氧化指标的效果。

Objective To evaluate the effect of Jiangzhiligan granules on cytochrome P450 2E1（CYP2E1） gene and protein expression of rat model with non-alcoholic fatty liver disease（NAFLD）, and investigate the mechanism of the drug. Methods SDF levels of 20 healthy Wistar rats were selected and established the NAFLD model. All of the rats were divided into the prevention group and model group by random number table method, with 10 in each group. Since the second week of model establishment; the rats in the prevention group were given Jiangzhiligan granules by gavage, 1 time daily, 6 g per kg body weight; while the model group was given equal amounts of normal saline by gavage; for 6 weeks in both of the two groups. The liver histopathology, liver function, serum lipid, oxidation indexes, levels of CYP2E1 m RNA and protein expression were compared between the two groups, and the effect of Jiangzhiligan granules on CYP2E1 gene and protein expression of rat model with NAFLD was summarized. Results The liver wet weight and liver indexes of the prevention group were lower than those in model group, the difference was statistically significant（P 0.05）. There was no significant difference of body mass index between the two groups（P 0.05）. Partial steatosis of hepatocytes in the prevention group was found, and its steatotic degree was lower than that of the model group, the difference was statistically significant（P 0.05）. Compared with 2 weeks after model establishment, the AST, ALT, TC, TG, HDL-C, LDL-C, MDA in the prevention group decreased significantly, and the SOD, GSH-PX, GSH increased significantly than those before the end of the experiment, the difference was statistically significant（P 0.05）. Before the end of the experiment, the levels of CYP2E1 m RNA and protein expression of liver tissue in the prevention group were lower than those in the model group, the difference was statistically significant（P 0.05）. Conclusion Jiangzhiligan granules could downgrade the CYP2E1 m RNA and protein in liver tissue of the rat model with NAFLD, and could improve the Liver function, blood lipid and oxidation index.