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硫普罗宁钠与硫普罗宁对小鼠急性肝损伤预防和治疗作用的比较
引用本文:李伟,徐桂清,韩玉谦,郝二军,薛长湖.硫普罗宁钠与硫普罗宁对小鼠急性肝损伤预防和治疗作用的比较[J].中国药理学与毒理学杂志,2009,23(6):450-455.
作者姓名:李伟  徐桂清  韩玉谦  郝二军  薛长湖
作者单位:1. 中国海洋大学食品科学与工程学院,山东,青岛,266003;河南师范大学化学与环境科学学院,河南,新乡,453007
2. 河南师范大学化学与环境科学学院,河南,新乡,453007
3. 中国海洋大学食品科学与工程学院,山东,青岛,266003
摘    要:目的观察并比较硫普罗宁钠(MPG-Na)及硫普罗宁(MPG)对急性肝损伤的预防和治疗作用。方法采用D-氨基半乳糖(Gal)(800mg.kg-1,ip)制备小鼠急性肝损伤模型。预防性给药时,分别ip给予小鼠MPG-Na或MPG37.5,75和150mg.kg-1,共7d,于最后一次给药后30min,用Gal染毒造模。治疗性给药时,在Gal染毒造模30min后分别ipMPG-Na或MPG37.5,75和150mg.kg-1,共2d。预防性给药小鼠Gal染毒24h、治疗性给药小鼠染毒48h后,检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、总蛋白(TP)、白蛋白(Alb)和Alb/球蛋白比值(A/G)。取肝脏组织,常规石蜡包埋,切片,HE染色,光镜下观察肝脏组织病理变化。结果与正常对照组比较,模型组小鼠血清GPT和GOT活性明显升高,肝脏组织出现明显的脂肪变性、肿胀或肝细胞变性坏死。预防性给予MPG-Na150mg.kg-1小鼠血清GPT和GOT活性与模型组比较显著降低,治疗性给予MPG-Na3个剂量血清GPT活性与模型组比较均明显降低,TP,Alb和A/G比值均无明显变化。预防性和治疗性给药后,肝脏组织病理损伤均明显减轻。另外,预防性和治疗性给药2种条件下,MPG-Na的作用与MPG相当。结论MPG-Na对Gal引起的急性肝损伤具有预防和治疗作用,与MPG作用相当。

关 键 词:硫普罗宁钠  硫普罗宁  D-氨基半乳糖  急性肝损伤
收稿时间:2008-12-24

Comparison of protective effects of N-(2-mercaptopropionyl)-glycine sodium and tiopronin against acute liver injury in mice
LI Wei,XU Gui-Qing,HAN Yu-Qian,HAO Er-Jun,XUE Chang-Hu.Comparison of protective effects of N-(2-mercaptopropionyl)-glycine sodium and tiopronin against acute liver injury in mice[J].Chinese Journal of Pharmacology and Toxicology,2009,23(6):450-455.
Authors:LI Wei  XU Gui-Qing  HAN Yu-Qian  HAO Er-Jun  XUE Chang-Hu
Institution:LI Wei1,2, XU Gui-Qing2, HAN Yu-Qian1, HAO Er-Jun1, XUE Chang-Hu1
Abstract:AIM To evaluate the prevention and treatment of N-(2-mercaptopropionyl)-glycine sodium (MPG-Na) and tiopronin (MPG) on acute liver injury. METHODS The experimental mouse model of hepatotoxicity induced by D-galactosamine (Gal) was applied to investigate preventive and remedial effects. In the preventive experiment, the mice were ip administered with MPG-Na or MPG 37.5,75 and 150 mg·kg~(-1), respectively, for 7 d. Gal 800 mg·kg~(-1) was ip given into the mice 30 min after the last administration. In the remedial experiment, the mice were ip given Gal 800 mg·kg~(-1) and 30 min later followed by MPG-Na or MPG 37.5, 75 and 150 mg·kg~(-1) , respectively, for 2 d. The mice were euthanized and serum was prepared 24 h (pre-treatment) or 48 h (post-treatment) after Gal injection. The activities of serum glutamyl pyruvic transaminase (GPT) and glutamyl oxaloacetic transaminase (GOT), the contents of total protein (TP) and albumin (Alb), and the Alb/globulin (A/G) ratio were determined. The liver tissues were collected for histopathological assessment (HE staining) under light microscope. RESULTS Compared with normal control group, the activities of serum GPT and GOT in model group were significantly increased. The injuries such as fatty degeneration and liver cell necrosis were observed. Compared with model group, the activities of GPT and GOT in pre-treatment groups were obviously decreased in MPG-Na 150 mg·kg~(-1) group. In post-treatment groups, the activity of GPT decreased in 3 MPG-Na groups. The contents of TP, Alb and A/G ratio had little change. In addition, MPG-Na alleviated the injuries such as fatty degeneration and liver cell necrosis obviously. Compared with MPG, MPG-Na showed similar effect. CONCLUSION MPG-Na has an obvious protective effect against Gal-induced acute liver injury in mice and the efficiency is equivalent as MPG.
Keywords:N-(2-mercaptopropionyl)-glycine sodium  tiopronin  D-galactosamine  acute liver injury
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