N-乙酰半胱氨酸对异烟肼和利福平联合应用所致小鼠肝损伤保护作用  

Protective the Treatment with Effect of N-acetylcysteine on Hepatic Damage Induced by the Combination of Isoniazid and Rifampicin in Mice

作　　者：袁保东 张炎林 陈国玺 刘小玉 姚芳 徐静[2] 王先松[2] 

机构地区：[1]武汉市结核病防治所,湖北武汉430030 [2]华中科技大学同济医学院,湖北武汉430030

出　　处：《武汉大学学报（医学版）》2016年第1期25-28,共4页Medical Journal of Wuhan University

基　　金：武汉市卫计委资助项目(编号:WX11C30)

摘　　要：目的:探讨N-乙酰半胱氨酸对异烟肼和利福平联用所致小鼠肝损伤的保护作用及其可能机制。方法:32只昆明鼠随机分为4组(每组8只)后给予如下治疗:腹腔注射异烟肼和利福平(肝损伤组)、腹腔注射N-乙酰半胱氨酸(NAC)30min后再腹腔注射异烟肼和利福平(NAC保护组)、腹腔注射NAC(NAC对照组)和腹腔注射生理盐水(对照组)。治疗14d后处死小鼠,取眼球血,测量血清谷氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性;取小鼠肝组织并测量肝指数(肝指数=肝重/体重),部分肝组织常规石蜡包埋切片,光镜观察肝组织形态结构特征;部分肝组织均浆,检测其中丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果:肝损伤组小鼠肝细胞呈不同程度的水变性和脂肪变性及局灶性坏死溶解,NAC保护组小鼠肝细胞呈轻度水变性和脂肪变性,未见肝细胞坏死。肝损伤组及NAC保护组小鼠肝指数(64.38±0.63及60.54±0.57)、血清ALT(82.81±4.75及68.70±5.81)U/L及AST活性(173.56±6.30及119.92±4.58)U/L显著高于对照组[57.48±0.53,(33.58±5.68)U/L、(85.84±5.20)U/L](P<0.01);NAC保护组小鼠肝指数、血清ALT及AST活性明显低于肝损伤组(P<0.01);与对照组(0.83±0.12、125.56±5.36)比较,肝损伤组小鼠MDA含量[(3.22±0.17)nmol/mgprot]显著升高,SOD活性[(88.44±5.52)U/mgprot]显著降低(P<0.01);与肝损伤组比较,NAC保护组MDA含量[(1.78±0.27)nmol/mgprot]明显降低,SOD活性[(106.85±3.66)U/mgprot]明显升高(P<0.01)。结论:异烟肼与利福平联合应用能引起小鼠较严重的肝损伤,N-乙酰半胱氨酸能够减轻这种损伤作用,其保护机制可能与增加机体谷胱甘肽(GSH)含量,从而减轻脂质过氧化反应有关。Objective：To investigate the protective action of N-acetylcysteine on hepatic damage caused by the treatment with the combination of isoniazid and rifampicin in mice.Methods：Kunming mice were injected intraperitoneally with saline（control）,N-acetylcysteine（NAC）,combination of isoniazid（I）and rifampicin（R）（I＋R）,or NAC and I＋R（NAC＋I＋R）once every day.Af-ter 14 days,the liver index（LI）,alanine aminotransferase（ALT）and aspartate aminotransferase（AST）activity in serum and the level of malondialdehyde（MDA）,superoxide dismutase（SOD）activity in liver tissues were measured respectively.Hepatic tissue morphology was observed under light microscope.Results：Macroscopic analysis revealed that coadministration of isoniazid and rifampicin led to severe liver tissue injury,including a wide range of hepatocellular vascular congestion,fatty change and local necrosis,whereas the administration of NAC produced a significant reduction of isoniazid and rifampicin-induced hepatotoxicity.The LI,ALT and AST activities in I＋R or NAC＋I＋R group were significantly elevated when compared with control group.The LI,activity of ALT and AST in serum,and MDA levels in liver tissues in NAC＋I＋R group were significantly lower than those in I＋R group,but the SOD activity in NAC＋I＋R group increased significantly in comparison with I＋R group.Conclusion：Co-administration of isoniazid and rifampicin was able to cause severe hepatic damage.Pre-administration of NAC reduced the side-effect induced by the treatment with the combination of isoniazid and rifampicin.NAC probably exerted its protective action by increasing glutathione（GSH）production,thereby decreasing lipid peroxidation.

关 键 词：N-乙酰半胱氨酸 异烟肼 利福平 损伤 肝脏保护 脂质过氧化 

分 类 号：R965[医药卫生—药理学] R52[医药卫生—药学]