山楂叶总黄酮对非酒精性脂肪性肝炎大鼠肝组织CYP2E1表达的影响

Effect of TFHL on expression of CYP2E1 in liver tissue of rats with NASH

目的:观察细胞色素P4502E1(CYP2E1)在高脂饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠肝组织中的表达及山楂叶总黄酮(TFHL)对其的影响。方法:以高脂饮食喂养12周建立NASH大鼠模型,分别以250、125mg/kg体质量/d的TFHL和195.4mg/kg体质量/d的易善复进行干预,观察大鼠肝组织的病理改变,肝组织匀浆MDA含量和SOD、GSH-Px的活性,RT-PCR和免疫组化法检测CYP2E1基因mRNA和蛋白在肝组织中表达。结果:①NASH模型组大鼠肝组织出现重度脂肪变、不同程度的炎细胞浸润及坏死灶,肝组织MDA含量较正常组大鼠显著增高,肝匀浆SOD、GSH-Px的活性明显降低,肝组织CYP2E1基因mRNA和蛋白表达显著增强。②肝组织CYP2E1基因的表达与MDA含量呈明显正相关,与SOD和GSH-Px活性则呈明显负相关。③TFHL高、低剂量组大鼠肝组织炎症活动程度、肝匀浆MDA含量、肝组织CYP2E1基因mRNA和蛋白表达均较模型组大鼠显著降低,而肝匀浆SOD、GSH-Px的活性则较模型组大鼠明显增高。结论:CYP2E1参与高脂饮食诱导的大鼠NASH的发生发展,TFHL能抑制CYP2E1活性,抑制肝组织脂质过氧化反应,提高肝细胞的抗氧化能力,从而防止NASH的进一步发展。

Objective： To observe the expression of cytochrome P4502E1 （CYP2E1） in the liver tissue of rats with non-alcoholic steatosis hepatitis （NASH） induced by high-fat diet, and effect of total flavonoids of Chinese hawthorn Ieaf（TFHL）. Methods： The model rats of NASH were induced by 12 weeks＇ high-fat diet, and treated with TFHL and Essentiale. The pathological changes of rats liver were observed, the amounts of liver MDA, and the activities of SOD, GSH-Px were detected, the mRNA and protein expressions of CYP2E1 were detected with RT-PCR and immunochemical method. Results： ①there were serious steatosis, different degree of infiltration of inflammatory cells and necrosis focus in the livers of model rats, the amounts of liver MDA was higher than that of the normal group, the acttivities of SOD, GSH-Px in the livers were lower, the expressions of mRNA and protein were strengthened.②the expression of CYP2E1 of livers has a positive correlation with the amount of MDA, but negative correlation with the activity of SOD and GSH-Px. ③the inflammation of liver, the amounts of liver MDA level, the mRNA and protein expressions of CYP2E1,the activity of SOD and GSH-Px in rats treated with high or low dose TFHL were obviously lower than the model rats, but the activities of SOD and GSH-Px were higher than the model rats.Conclussion： CYP2E1 takes part in the onset and development of NASH induced by high-fat diat, TFHL can restrain the activity of CYP2E1 and the lipid peroxidization, enhance the ability of antioxygenation of liver cells, and prevent the further development of NASH.