目的 探讨甘草次酸衍生物（TY501）对四氯化碳（CCl₄）致小鼠肝纤维化的保护作用及其机制。方法 采用经典CCl₄造模法建立小鼠肝纤维化模型，给予高、中、低剂量（45、15、5 mg/kg）TY501干预治疗，用秋水仙碱（0.36 mg/kg）作阳性对照。给药30 d后，检测各组小鼠肝功能指标、肝纤维化指标、肝组织羟脯氨酸（Hyp）和转化生长因子-β1（TGF-β1）的量，并取其肝组织进行病理学染色。结果 与模型组相比，TY501各治疗组肝功能指标（ALT、AST、ALP、ALB）、肝纤维化指标（HA、LN、PCⅢ、CIV）及肝组织Hyp、TGF-β1的量均有不同程度改善，其中高剂量组改善作用最为明显（P<0.05、0.01）；肝组织病理学切片显示，给药组小鼠肝纤维化程度降低，有逆转趋势。结论 TY501对CCl₄造成的肝纤维化有明显的保护作用。

Objective To explore the protective effects of glycyrrhetic acid derivatives (TY501) on carbon tetrachloride-induced liver fibrosis in mice. Methods The mice liver fibrosis was established by classical CCl₄, and TY501 was given in three kinds of dosage (45, 15, and 5 mg/kg), with colchicine serving as control. After 30 d treatment, the liver function, fibrosis and the levels of Hyp and TGF-β1 were detected. Moreover, the histopathological changes were detected by HE and Masson staining. Results Compared with model group, the levels of ALT, AST, ALP, ALB, HA, LN, PCⅢ, CIV, Hyp, and TGF-β1 were all decreased, with high-dose group being the most significant (P < 0.05, 0.01). Histopathological examination showed that liver fibrosis of those mice treated with TY501 was improved to some extent. Conclusion TY501 can significantly protect carbon tetrachloride-induced hepatic fibrosis.

国家自然科学基金资助项目（81503130）；天津市应用基础与前沿技术研究计划（14JCQJC13000）；天津市应用基础与前沿技术研究计划（13JCZDJC28500）