【摘要】 目的探讨肝脏脂质过氧化反应和肝药酶活性改变与抗结核药物肝毒性的关系。方法健康成年SD大鼠56只,随机分为7组:INH(isoniazid,H)组、RFP(rifampicin,R)组、PZA(pyrazinamide,Z)组、HR组、RZ组、HRZ组和生理盐水对照组。分别灌药10 d后处死大鼠,取肝脏切片,电子显微镜下观察肝脏病理变化,制备肝匀浆测定MDA(Maleic Dialdehyde)、SOD(Superoxide Dismutase)、GSH(reducedglutathione)和P450含量。结果各实验组MDA和P450均有不同程度升高,SOD和GSH有不同程度降低,肝脏病理变化与脂质过氧化反应、肝药酶有相关性。结论异烟肼、利福平、吡嗪酰胺均可引起大鼠的脂质过氧化指标的改变及肝脏细胞的病理损害,多种药物联用比单用改变明显;抗结核药物肝脏毒性与脂质过氧化反应程度关系密切,吡嗪酰胺组比其他单用药组肝脏毒性大。利福平有明显肝药酶诱导活性。更多还原

【Abstract】 Objective To study the correlation of lipid peroxidation,P450 drug-metabolizing enzyme of liver tissue and hepatotoxicity.?Methods Fifty-six healthy adult rats were divided randomly into 7 groups: INH(H),RFP(R),PZA(Z),HR,RZ,HRZ,the control group.The rats took different drugs and same foods for 10 days,and then were taken the livers.The livers were cut into slices and watched pathologic changes of hepatic cells under electronic microscope,were homogenized and measured MDA,GSH,SOD,P450.?Results MDA and P450 increased,while GSH and SOD decreased in each drug group.In the groups contained RFP,level of P450 increased significantly.The degree of liver damage and the change of index of lipid peroxidation were more severe in the combined antituberculous drug groups than that in the single antituberculous drug groups.The hepatic pathologic damage was related with the degree of lipid peroxidation.?Conclusion INH,RFP,PZA all could induce the lipid peroxidation and hepatic damage.更多还原