细胞色素P450 2E1在脂肪性肝炎大鼠肝组织的表达及作用

目的探讨细胞色素P4502E1(CYP2E1)在脂肪性肝炎大鼠肝组织内的表达和作用。方法通过高脂饮食和逐渐增加酒精灌胃量持续16周建立Wister大鼠脂肪性肝炎动物模型,造模结束时检测模型组和正常组动物血脂、游离脂肪酸(FFA)和肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、还原性谷胱甘肽(GSH)含量;免疫组化标记检测肝组织CYP2E1表达;RT-PCR法检测CYP2E1 mRNA的水平。结果实验结束时,模型组大鼠血脂和血清FFA较正常组显著增高(P<0.01);肝组织MDA较正常组显著增高(P<0.01),而SOD和GSH较正常组明显减低(P<0.01);肝组织内CYP2E1及其基因表达较正常组显著升高(P<0.01),并与肝组织内MDA、脂肪变程度、炎症计分呈明显正相关(r值分别为0.652,0.913和0.943,P值均<0.05),与SOD、GSH呈显著负相关(r值分别为-0.916,-0.766,P<0.01)。结论脂肪性肝炎大鼠肝脏内CYP2E1呈诱导表达状态,后者可能通过增强氧应激,降低抗氧化能力,加重脂质过氧化等过程参与了脂肪性肝炎的形成。

The expression of cytochrome P450 2E1 in liver tissues in rats with steatohepatitis

Objective To investigate the expression and effects of cytochrome P450 2E1 in rats with steatohepatitis. Methods Steatohepatitis model was established by feeding high fat diet and increasingly intragastric perfusion of ethanol in rats for 16 weeks. Blood lipids, free fatty acid in serum and the malonaldehyde, superoxide dismutase and glutathione in liver were measured respectively; CYP2E1 and its mRNA in liver specimens were detected by immunohistochemistry and RT-PCR, respectively. Results Blood lipids ,serum free fatty acid in rats with steatohepatitis was markedly increased (P<0.01); the level of malonaldehyde increased significantly(P<0.01), whereas superoxide dismutase and glutathione concentration was markedly decreased in model group (P<0.01). The expression of CYP2E1 and its mRNA was enhanced significantly(P<0.01) in rats with steatohepatitis. Conclusion CYP 2E1 increases in rat with steatohepatitis, which might improve oxygen stress, decrease anti-oxygen ability and aggravate lipid peroxidation.