来氟米特对急性化学性肝损伤小鼠肝Cyt.P450酶含量及CYP2E1 mRNA表达的影响  

Effect of Leflunomide on the content of cytochrome P450 enzyme and CYP2E1 mRNA expression of mice with acute chemical injury

作　　者：郭安平[1] 李俊[1] 吕雄文[1] 司洪芳[1] 

机构地区：[1]安徽医科大学药学院,合肥230032

出　　处：《安徽医科大学学报》2008年第1期58-61,共4页Acta Universitatis Medicinalis Anhui

基　　金：高等学校博士学科专项科研基金(编号:20050366003)

摘　　要：目的观察来氟米特(Lef)作用前后急性化学性肝损伤小鼠肝微粒体细胞色素P450(Cyt.P450)、细胞色素b5(Cyt.b5)含量及P4502E1(CYP2E1)mRNA表达水平的变化,进一步研究其治疗机制。方法采用CCl4诱导小鼠急性化学性肝损伤模型,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,肝匀浆丙二醛(MDA)、谷胱甘肽(GSH)含量以及肝微粒体细胞色素P450(Cyt.P450)和细胞色素b5(Cyt.b5)含量,RT-PCR法检测小鼠肝脏细胞色素P4502E1(CYP2E1)mRNA表达水平,并作肝组织切片病理观察。结果Lef明显降低CCl4急性肝损伤小鼠血清ALT、AST水平;降低肝匀浆MDA含量;提高GSH含量并提高肝微粒体Cyt.P450、Cyt.b5含量;抑制CYP2E1 mRNA表达;减轻肝脏病理损伤。结论Lef治疗CCl4所致小鼠急性化学性肝损伤,可能与其诱导肝微粒体Cyt.P450表达,抑制CYP2E1 mRNA转录及抗脂质过氧化有关。Objective To investigate the effect of Leflunomide （Lef） on content of Cyt. P450 and CYP2E1 mRNA expression of mice with acute chemical linjury and its possible therapeutic mechanism. Methods A liver injury model was induced by CCl4. The levels of amino transferase （ALT） ,aspartic transaminase（AST） in plasma, the contents of malondiadehyde （MDA） ,glutathione （GSH） in liver homogenate and Cyt. P450 ,Cyt. b5 contents in hepatic microsomal were measured. RT-PCR method was applied to determine the expression of CYP2E1 mRNA. Hepatic pathological examination was observed. Results Lef significally lowered serum transaminase （ALT, AST）levels, decreased MDA content and improved GSH level in liver homogenate as well as inducing an increase in the contents of hepatic microsomal Cyt. P450, Cyt. b5. Lef also inhibited the expression of CYP2E1 mRNA and reduced the pathological damage on liver. Conclusion It is suggested that the therapeutic effects of the Lef might be related to induction of hepatic microsomal Cyt. P450,inhibiting the expression of CYP2E1 mRNA and its inhibition of lipid peroxidation.

关 键 词：肝疾病/化学诱导 肝疾病/治疗 细胞色素P450酶系统 细胞色素P450 CYP2E1 异恶唑类 

分 类 号：R345.99[医药卫生—基础医学] R977.3