甘草酸对实验性肝内胆汁郁积大鼠的预防和治疗作用

目的：探讨甘草酸（glycyrrhizin，GL）和地塞米松（dexamethasone，DEX）对α-萘异硫氰酸（alphanaphthylisothiocyanate，ANIT）致急性肝内胆汁郁积型肝炎的作用。方法：应用ANIT制造大鼠急性肝内胆汁郁积型肝炎模型，分别应用GL和DEX进行预防性和治疗性给药，观察GL和DEX对大鼠肝功能生化指标、肝组织病理改变、2h胆汁流量和酮洛芬葡萄糖醛酸结合物（ketoprofen glucuroide，KPG）的累计胆排泄率的影响。结果：DEX预防性给药明显减轻胆管损伤，对肝细胞损伤无保护作用。ANIT染毒后3h给予DEX不能减轻胆汁郁积，染毒后12h给予DEX使肝细胞损伤加重。预防性给予GL和染毒后3h给予GL均能明显减轻胆汁郁积和肝细胞损伤。结论：在实验性急性肝内胆汁郁积型肝炎早期，GL具有明显的预防和治疗作用。

Protective effect of glycyrrhizin on acute cholestasis induced by alpha-naphthylisothiocyanate in rats

AIM: To investigate the effects of glycyrrhizin(GL)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 GL and DEX on acute cholestasis were examined by serology determination, histological assessment of hepatic injury and bile excretion experiments. RESULTS: The protection of DEX pretreatment was directed toward cholangiocytes rather than hepatocytes. Rats remedially treated with DEX 3 h after ANIT administration were not resistant to ANIT toxicity. Notably, remedial treatment with DEX 12 h after ANIT enhanced ANIT toxicity. However, GL attenuated both bile duct and hepatocyte damage induced by ANIT in the initial phase of impairment. CONCLUSION: GL exhibited better protection against ANIT-induced acute cholestasis than DEX. In the initial phase of impairment of acute cholestasis, the protection of GL maybe partially due to modifications of metabolism and excretion of ANIT and anti-inflammatory effect.