槲皮素对异烟肼联用利福平致大鼠肝损伤的防护作用

Protective Effects and Mechanisms of Quercetin on Hepatic Injury Induced by Isoniazid Combined with Rifampicin in Mice

目的观察槲皮素对异烟肼(INH)和利福平(RFP)联用致大鼠肝损伤的防护作用,并探讨其作用机制。方法选择雄性Wistar大鼠50只,自由进食饲料和水,适应性喂养1周后,按随机数字表法分为空白对照组,肝损伤模型组和槲皮素低、中、高剂量组,各10只。除空白对照组外,其余组大鼠每天一次性给予异烟肼和利福平各75 mg/kg,用药4周制备大鼠肝损伤动物模型,空白对照组仅给予等体积生理盐水,槲皮素低、中、高剂量组给予INH和RFP 2 h后,分别给予低、中、高剂量(50,100,200 mg/kg)槲皮素,空白对照组和肝损伤模型组均灌胃等体积的蒸馏水。4周后,测定大鼠血清中天门冬酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和总胆红素(TBIL)的水平,肝脏指数,以及肝组织匀浆中的丙二醛(MDA)、谷胱甘肽(GSH)水平和超氧化物歧化酶(SOD)的活性,并作肝组织病理学检测。结果槲皮素能降低大鼠肝脏指数,AST,ALT和TBIL及肝匀浆中MDA水平,升高肝匀浆中GSH及SOD水平(P<0.05),还能减轻肝组织变性和坏死程度,缓解肝组织损伤的病理改变。结论槲皮素对INH和RFP联用所致大鼠肝损伤有保护作用,其作用机制可能与槲皮素抑制脂质过氧化反应有关。

Objective To investigate the protective effect and mechanism of quercetin on liver injury induced by isoniazid（ INH） combined with rifampicin（ RFP） in rats. Methods Totally 50 male Wistar mice were fed with feed and water,and 1 week after adaptive feeding,the mice were randomly divided into blank control group,liver injury model group and quercetin low,middle and high dose groups,10 mice in each group. In addition to the blank control group,the mice in the other groups were given INH and RFP（ each75 mg/kg） per day for 4 weeks to prepare the animal models of liver injury in mice,and the blank control group was given equal volume of normal saline,2 h after giving INH and RFP,the low,middle and high dose groups were given low dosage,middle dosage and high dosage of quercetin（ 50,100,200 mg/kg）,the blank control group and the liver injury model group were filled with equal volume of distilled water. The serum levels of AST,ALT and TBIL,liver index,contents of MDA,GSH,and SOD in liver were measured after4 weeks of giving quercetin,and the hepatic pathological changes were also observed. Results Quercetin could reduce the liver index,the serum level of AST,ALT,TBIL and the content of MDA,raise the liver GSH content,promote the the activities of SOD in liver in mice. The degeneration and necrosis of liver tissue were relieved,and the pathological changes of liver tissue injury were alleviated.Conclusion Quercetin has the protective effect on the hepatotoxicity induced by INH combined with RFP in mice,and the mechanism may be related to the inhibition of lipid peroxidation of quercetin.