利福平异烟肼合用致小鼠肝毒性增加的机理研究

Study On the Mechanisms of Increased Hepatotoxicity of Rifampicin Plus Isoniazid in mice

目的 观察比较利福平 (RFP)与异烟肼 (INH)单用及合用对小鼠肝脏的致伤作用 ,探讨两药合用肝毒性增加的作用机理。方法 分别测定血清谷丙转氨酶 (ALT)的活性 ,肝匀浆中谷胱甘肽 (GSH)、丙二醛 (MDA)的含量 ,肝微粒体中细胞色素P4 5 0及其亚型 2E1的活性 ;在显微镜下观察肝组织病理形态学变化。结果 两药合用组的ALT水平、MDA含量以及细胞色素P4 5 0和P4 5 0 2E1的活性均明显高于对照组及单一用药组 ,而GSH含量明显降低。结论 RFP与INH合用肝毒性增加不仅与过氧化反应增强有关 ,而且还与细胞色素P4 5 0 2E1活性增加有关。

Aim To observe the hepatotoxic effects induced by Rifampicin (RFP) and Isoniazid (INH) when used alone or in combination on mice.Methods The serum level of ALT,liver index, contents of malondialdehyde (MDA) and glutathione (GSH),activity of microsomal cytochrome P450 and its isoform P4502E1 in liver were measured.The degree of liver injury was observed by light microsocope.Results The combination of RFP and INH markely elevated liver index,serum ALT,liver MDA and microsomal cytochrom P450,its isoform P4502E1 and reduced the liver GSH,compared with the control and RFP or INH used alone.Conclusion The increased hepatotoxic effects of RFP and INH in combination treament on mice suggest that the hepatotoxic injury may be related to the enhanced lipid peroxidation and to the increased activity of microsomal cytochrome P4502E1