异烟肼利福平合用致大鼠肝损伤的实验模型  

Study on liver injury induced by isoniazid and rifampicin in rats

作　　者：杨慧媛[1] 宋育林[1] 许建明[1] 胡乃中[1] 查正伟[1] 王道斌[2] 

机构地区：[1]安徽医科大学第一附属医院消化科、安徽省消化系统疾病重点实验室 [2]安徽医科大学第一附属医院中心实验室,合肥230022

出　　处：《安徽医科大学学报》2008年第2期185-189,共5页Acta Universitatis Medicinalis Anhui

摘　　要：目的观察异烟肼、利福平单用与合用致大鼠肝损伤的情况并探讨其与脂质过氧化的关系。方法50只♂W istar大鼠,随机分为正常对照组、异烟肼+利福平组(RH组)及异烟肼组(H组),分别给予0.9%氯化钠注射液10m l/(kg·d)、异烟肼50 mg/(kg·d)+利福平50 mg/(kg·d)、异烟肼50 mg/(kg·d),每日一次定时空腹灌胃。第14天和28天分批处死大鼠,观察大鼠肝脏病理形态变化,检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TB IL)、直接胆红素(DB IL)水平以及肝组织匀浆丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽-过氧化物酶(GSH-PX)活力变化。结果与对照组比较,RH组大鼠血清转氨酶、胆红素升高差异有显著性,H组大鼠血清转氨酶升高差异也有显著性,但胆红素升高差异无显著性。与第2周RH组比较,第4周RH组胆红素有下降趋势,但差异无显著性。与第4周RH组比较,异烟肼组大鼠血清AST、TB IL、DB IL升高差异有显著性。与正常对照组比较,仅RH组大鼠肝匀浆MDA升高、SOD、GSH-PX降低差异有显著性,与第4周RH组比较,异烟肼组MDA升高、SOD、GSH-PX降低差异有显著性。与正常对照组比较,RH组和H组大鼠肝脏炎症活动度计分增加,但仅RH组差异有显著性。结论异烟肼和利福平两药合用肝毒性较单用异烟肼明显,两药合用的肝毒性并未随时间延长而加重。异烟肼和/或利福平致肝损伤作用机制可能与脂质过氧化增加有关。Objective To observe liver injury induced by isoniazid and rifampicin in rats and explore its relation-ship with lipid peroxidation. Methods Fifty male Wistar rats were randomly divided into normal control group, isoniazid ＋ rifampicin group （ RH group） and isoniazid group （ H group ）, treated with 0. 9% sodium chloride 10 ml/ （kg·d）, isoniazid 50mg/（kg·d） ＋ rifampicin 50 mg/（kg·d） and isoniazid 50 mg/（ kg·d） respectively by intragastric administration on an empty stomach. The rats were killed on 14th day and 28th day. Histological analysis was carried out to assess the injury of the liver. Serum ALT, AST, TBIL, DBIL and liver tissues homogenate MDA, SOD, GSH-PX were measured. Results Compared with normal control group, serum ALT, AST, TBIL, DBIL in RH groups were obviously elevated, and serum ALT, AST in H group were also obviously elevated, but there was no significant difference of TBIL, DBIL. Compared with RH group of week 2, Serum TBIL, DBIL of RH group of week 4 decreased, but there were no significant difference between two groups. Compared with H group, Serum AST ,TBIL, DBIL of RH group of week 4 were significantly elevated. Compare with normal control group, Only liver tissues homogenate MDA in RH group was significantly increased, simultaneously with decrease on liver tissues homogenates SOD, GSH-PX also. Compare with H group, liver tissues homogenate MDA in RH group of week 4 was significantly increased, simultaneously with decrease on liver tissues homogenates SOD, GSH-PX also. Compare with normal control group, scores of hepatic inflammation in RH group and H group increased, but there was significant difference between RH group and normal control group. Conclusion The hepatotoxicity induced by combination of isoniazid and rifampicin is more serious than that by isoniazid used alone, the hepatotoxicity induced by combination of the two drugs didn＇t aggravate with administration time prolonged. Liver injury mechanism induced by isoniazid and/or rifampicin may be relat

关 键 词：异烟肼/副作用 利福平/副作用 肝/病理学 脂质过氧化/作用 大鼠 

分 类 号：R575.1[医药卫生—消化系统] R978.19[医药卫生—内科学]