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甘草酸、甘草次酸及苦参碱等对实验性胆汁淤积大鼠作用的比较

Protective effect of glycyrrhizin acid,glycyrrhetinic acid and matrine on acute cholestasis induced by alpha-naphthylisothiocyanate in rats

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【作者】 赵营张玉林徐林刚陈西敬俞巧玲

【Author】 ZHAO Ying1,2,ZHANG Yu-lin2,XU Lin-gang2,CHEN Xi-jing1,YU Qiao-ling11Center of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009;2Xinxiang Medical College,Xinxiang 453003,China

【机构】 中国药科大学药物代谢与动力学研究中心新乡医学院中国药科大学药物代谢与动力学研究中心 南京210009新乡453003南京210009

【摘要】 目的:观察甘草酸(GL)、甘草次酸(GA)、苦参碱(MT)、氧化苦参碱(OMT)、丹参酚酸B(SAB)、水飞蓟素(SI)和地塞米松(DEX)对异硫氰酸-1-萘酯(ANIT)致急性肝内胆汁淤积的作用。方法:应用灌胃ANIT(50 mg/kg)建立大鼠急性肝内胆汁淤积病理模型,观察上述药物对大鼠肝功能各项生化指标、肝组织病理改变、2 h胆汁流量和酮洛酚葡萄糖醛酸结合物(KPG)的累计胆排泄率的影响。结果:GL、GA和MT均能明显减轻ANIT导致的胆管损伤、胆汁淤积和肝细胞损伤。DEX减轻胆管损伤,对肝细胞损伤无保护作用。OMT、SAB和SI不能减轻ANIT的肝脏毒性。结论:GL、GA、MT和DEX对ANIT诱导的急性肝内胆汁淤积型肝炎有明显的保护作用,而且GL、GA和MT的保护作用优于DEX。

【Abstract】 Aim:To investigate the effects of glycyrrhizin acid(GL),glycyrrhetinic acid(GA),matrine(MT),oxymatrine(OMT),salvianolic acid B(SAB),silymarin(SI) and dexamethasone(DEX) on alpha-naphthylisothiocyanate(ANIT)-induced acute cholestasis in rats.Methods:Acute cholestasis in rats was induced by ANIT,and the effects of these medicines on cholestasis were examined by serological determination,histological assessment of liver damage and bile excretion experiments.Results:The administration of GL,GA,or MT could ameliorate hepatocyte injury and ANIT induced cholestasis,as evidenced by serological and histological findings.Furthermore,the bile flow and the accumulative bile excretion of ketoprofen glucuroide(KPG) extremely suppressed by ANIT were significantly ameliorated in ANIT-intoxicated rats with the administration of GL,GA,or MT.Rats could be protected against ANIT-induced acute cholestasis with DEX administration.Notably,distinguished from GL,GA and MT,DEX could not reduce the elevated serum levels of alanine aminotransferase(ALT) and hepatocyte necrosis caused by ANIT.In contrast,rats given OMT,SAB or SI were not resistant to ANIT toxicity.Conclusion:The protective effect of DEX is directed toward cholangiocytes rather than hepatocytes,and the natural products(GA,GL and MT) exhibit better protective effects against ANIT-induced cholestasis than DEX.

【基金】 国家自然科学基金资助项目(No.30472060)~~
  • 【文献出处】 中国药科大学学报 ,Journal of China Pharmaceutical University , 编辑部邮箱 ,2007年03期
  • 【分类号】R285
  • 【被引频次】23
  • 【下载频次】541
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