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机构地区:[1]武汉市结核病防治所内科,武汉430030 [2]华中科技大学同济医学院病理学系,武汉430030
出 处:《医药导报》2016年第7期724-727,共4页Herald of Medicine
基 金:武汉市科技局资助项目(WX08C15);武汉市科技局资助项目(WX11C30)
摘 要:目的探讨N-乙酰半胱氨酸(NAC)对利福平致肝损伤小鼠的保护作用及其机制。方法将32只昆明种小鼠随机分为4组(每组8只):模型对照组(腹腔注射利福平造模)、NAC治疗组(造模,腹腔注射NAC)、NAC对照组(腹腔注射NAC)与正常对照组(腹腔注射0.9%氯化钠溶液)。14 d后测量小鼠血清丙氨酸氨基转移酶(ALT)活性、天冬氨酸氨基转移酶(AST)活性、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性,测量肝指数,光镜观察肝组织形态结构特征。结果模型对照组小鼠肝细胞呈不同程度水变性和脂肪变性及局灶性坏死溶解,NAC治疗组小鼠肝细胞呈轻度水变性和脂肪变性,未见肝细胞坏死。模型对照组与NAC治疗组小鼠肝指数、血清ALT及AST活性显著高于正常对照组(P<0.01);NAC治疗组小鼠肝指数、血清ALT及AST活性明显低于模型对照组(P<0.01)。与正常对照组比较,模型对照组小鼠MDA含量显著升高,SOD活性显著降低(P<0.01);与模型对照组比较,NAC治疗组MDA含量明显降低,SOD活性明显升高(P<0.01)。结论利福平可诱导小鼠较严重肝损伤,NAC能够减轻该损伤。Objective To investigate the role of N-acetylcysteine as a protective agent in rifampicin-induced hepatic injury of mice. Methods Thirth-two Kunming mice were randomly divided into four groups(n=8 each).The mice in each group were injected intraperitoneally with 0.9% sodium chloride solution (control), N-acetylcysteine (NAC), combination of rifampicin (R), or NAC and R (NAC+R) once every day.After 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 rifampicin led to severe liver tissue injury,including a wide range of hepatocellular vascular congestion,fatty change and local necrosis, whereas the administrationof NAC produced a significant reduction of rifampicin-induced hepatotoxicity .LI,ALT and AST activities in R or NAC+R group were significantly elevated as compared with the control group(P〈0.01) .LI, activities of ALT and AST in serum,and MDA levels in liver tissues in NAC+R group were significantly lower than those in R group ( P〈0.01) ,but the SOD activity in NAC+R group was increased significantly in comparison with R group (P〈0.01). Conclusion Rifampicin was able to cause severe hepatic injury.Pre-administration of NAC reduced the side-effect induced by the treatment with the rifampicin.
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