凯西莱对四氯化碳致小鼠肝毒性保护作用的研究

Protective effects of tiopronin on carbon tetrachloride-induced hepatotoxicity in mice

目的 :研究凯西莱对四氯化碳 (CCl4 )致小鼠肝毒性的保护作用及其机理 ,并探讨其剂量学。方法 :采用 CCl4 腹腔注射制备小鼠急性肝损伤模型 ,随机分为 4组 ,以不同剂量凯西莱 (2 5 ,5 0 ,10 0及 2 0 0 mg· kg- 1·d- 1 )腹腔注射治疗 4天。观察动物体重改变及肝组织超微结构改变 ,检测血清丙氨酸氨基转移酶 (AL T)、天门冬氨酸氨基转移酶 (AST)活性及肝脏蛋白、丙二醛 (MDA)、还原型谷胱甘肽 (GSH)和超氧化物歧化酶 (SOD)水平。结果 :CCl4 注射后小鼠体重不增 ,血清 AL T、AST和肝脏 MDA水平明显升高 ,肝脏 GSH和 SOD水平则降低 ,肝组织超微结构显示有明显损伤。凯西莱治疗组与模型组相比 ,血清 ALT和 AST活性及肝组织 MDA含量均显著降低 ,以 5 0 mg/ kg治疗组肝损伤最轻。凯西莱还可使肝脏 GSH和 SOD恢复到正常水平。结论 :凯西莱通过抗脂质过氧化而有效对抗 CCl4 对小鼠的肝毒性 ,且存在最佳剂量。

Objectives:To investigate the hepatoprotective effects and mechanisms of tiopronin on carbon tetrachloride(CCl 4)-induced hepatotoxicity in mice,and the optimal dosage of tiopronin was also studied.Methods:Mouse model of acute liver damage was established by injection of CCl 4 intraperitoneally.The CCl 4 treated-mice were divided randomly into four groups and treated with tiopronin at the doses of 25,50,100,and 200 mg·kg -1·d -1 for 4 days respectively.Changes of body weight and hepatic ultrastructures were observed.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST) activities were measured,and hepatic protein,malondialdehyde(MDA),reduced glutathione(GSH) and superoxide dismutase(SOD) levels were also determined.Results:CCl 4 treated-mice manifested no growth of body weight.Levels of serum ALT,AST and hepatic MDA in the model group significantly in creased,while hepatic GSH and SOD decreased.Moreover,obvious ultrastructural changes were observed in the CCl 4 treated-mice.Serum ALT,AST and hepatic MDA were significantly lower in the mice treated with both CCl 4 and tiopronin than those treated with CCl 4 alone.The slightest liver injury was found in the group treated with tiopronin at the dose of 50mg·kg -1.Hepatic GSH and SOD returned to normal level with the treatment of tiopronin.Conclusions:Tiopronin possesses potent protective effects against CCl 4-induced hepatotoxicity in mice by anti-lipid peroxidation,and there is an optimal dosage for its hepatoprotective effects.