目的 探讨别隐品碱（allocryptopine）对实验性肝纤维化的防治作用。方法 采用CCl₄复合因素诱导大鼠肝纤维化与血吸虫致小鼠肝纤维化模型，观察别隐品碱在造模同时（预防给药）和造模后（治疗给药）给药对脏器指数、肝功能、纤维化血清指标、脂质过氧化指标、肝组织胶原（CoI、CoIII）及羟脯氨酸（Hyp）表达的影响，并进行肝脏病理学检查。结果 对CCl₄所致肝纤维化大鼠模型，各剂量别隐品碱预防给药均能不同程度地降低肝指数及CoI表达（P＜0.05、0.01），其中高剂量明显降低CoIII表达（P＜0.01），中剂量明显降低脾指数、丙氨酸氨基转移酶（AST）的量（P＜0.05）；别隐品碱治疗组大鼠的肝指数、天冬氨酸氨基转移酶（ALT）的量、CoIII表达明显降低（P＜0.05、0.01）；预防给药与造模后给药均不同程度地减轻模型大鼠肝纤维化程度。对血吸虫致肝纤维化小鼠模型，别隐品碱预防给药显著降低小鼠ALT的量与Hyp水平（P＜0.05），高剂量别隐品碱治疗给药能明显降低肝指数，降低血清PCIII、碘透明质酸（HA）、ALT的量（P＜0.05、0.01），中剂量组肝指数、PCIII、HA的量明显降低（P＜0.05）；治疗给药组大鼠肝脏病变明显减轻。结论 别隐品碱对实验性肝纤维化大鼠有较好的保护肝细胞、改善肝功能、抗肝纤维化作用。

Objective To investigate the prophylactic and therapeutic effects of allocryptopine on experimental hepatic fibrosis. Methods Experimental hepatic fibrosis models were induced by injection of tetrachloride in combination with the drinking of 5% alcohol to rats and Schistosoma japomicum infection to mice. The effects of allocryptopine anti-hepatic fibrosis were evaluated by comparing the liver and spleen indexes, tissue biochemical indices (ALT, AST), lipid peroxidation indices (GSH-P_X, MDA, SOD), serum fibrosis indices (HA, PCIII LN), the expression level of Hyp and collagen type I, III (CoI, CoIII), and the liver pathology before and after allocryptopine intervention. Results In CCl₄-induced liver fibrosis model rats, compared with model group, the liver index and the expression level of CoI were obviously decreased in allocryptopine prophylactic groups (P<0.05, 0.01), high-dose prophylactic allocryptopine could significantly reduce the expression level of CoIII (P<0.01), middle-dose prophylactic allocryptopine could obviously reduce the spleen index, the content of AST (P<0.05); in allocryptopine therapeutic group, the liver index, the content of ALT, and the expression level of CoIII were significantly decreased (P<0.05, 0.01). In S. japomicum-induced liver fibrosis model mice, prophylactic allocryptopine could reduce the content of ALT and the expression level of Hyp (P<0.05); the liver index, the contents of PCIII, HA, and ALT were significantly decreased in high-dose allocryptopine therapeutic group (P<0.05, 0.01), the liver index, the contents of PCIII, and HA were obviously decreased in middle-dose allocryptopine therapeutic group (P<0.05); In addition, the hepatic histopathology was also improved in varying degrees after allocryptopine intervention. Conclusion Allocryptopine has certain effects on anti-injury for hepatocyte, ameliorating liver function, and prohibiting hepatic fibrosis.

科技部国际科技合作计划(2009DFA31270)