硫普罗宁对大鼠酒精及四氯化碳致肝纤维化的保护作用

Tiopronin protects rats against liver fibrosis induced by alcohol and carbon tetrachloride

目的:观察硫普罗宁对酒精及四氯化碳致大鼠肝纤维化的保护作用。方法:40只健康雄性Wistar大鼠随机分为4组:正常对照组,模型组,硫普罗宁组和茴三硫阳性对照组,每组10只。给药组分别灌胃硫普罗宁100 mg.kg-1.d-1和茴三硫20 mg.kg-1.d-1,qd,共给药4周。除正常组外,其余3组大鼠每周2次灌胃白酒10 mL.kg-1,1 h后腹腔注射CCl4与花生油1∶3混合的液体0.25 mL.kg-1。第2周末、第4周末分别取血检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)等指标;第4周末进行肝组织病理检验。结果:与正常对照组比较,模型组血清ALT,AST和ALP显著升高(P<0.01),全血GSH-Px水平显著降低,血浆MDA水平升高(P<0.01),组织学出现肝脏纤维化表现;硫普罗宁和茴三硫均显著逆转这些指标的改变并改善肝纤维化,硫普罗宁的改善作用强于茴三硫(P<0.05)。结论:硫普罗宁对大鼠酒精及四氯化碳致肝纤维化有显著的保护作用,其机制可能与抑制脂质过氧化反应有关。

Objective ： To observe the protective effect of tiopronin on liver fibrosis induced by alcohol and carbon tetrachloride in rats. Methods： Male Wistar rats （n =40） wore randomly assigned to four groups. Tiopronin （ 100 mg.kg^-1.d^-1 ） or anetholtrithione （ 20 mg.kg^-1.d^-1 ） was orally administered once daily for 4 weeks. The liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride （0.25 mL. kg^-1 ） 1 h after intra- gastrical adminitration of 56% alcohol （ 10 mL.kg^-1 ） , twice a week. Serum levels of ALT, AST and ALP, whole blood glutathione peroxidase （GSH-Px） , and plasma malondialdehyde （MDA） were determined at the end of the 2 nd and 4 th week. The histopathologic alterations in the liver were observed at the end of 4 th week. Results： As compared with the normal rats, the levels of ALT, AST, ALP and MDA were significantly increased（P 〈 0.01 ） , and the GSH-Px level was decrease （P 〈 0.01 ） in the rats with liver fibrosis. Both tiopronin and anethohrithione markedly reversed the changes in these parameters, and ameliorated the pathological alterations of fibrosis in the liver. The protective effect of tiopronin was superior to that of anetholtrithione （P 〈 0.05）. Conclusions ： Tiopronin can protect rats against liver fibrosis induced by alcohol and carbon tetrachloride; the mechanism may relate to inhibition of hyperoxidation of lipids.