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目的:研究甘草酸铵联合苦参素对四氯化碳(CCl_4)导致的大鼠肝纤维化的抑制作用,并探讨其相关机制。方法:SD大鼠随机分为6组,每组10只,分别为正常组,模型组,秋水仙碱阳性药组(2 mg·kg~(-1)),甘草酸铵组(15 mg·kg~(-1)),苦参素组(30 mg·kg~(-1)),甘草酸铵联合苦参素(15 mg·kg~(-1)+30 mg·kg~(-1))组,除正常组外,其余各组均采用CCl_4诱导的大鼠肝纤维化模型,治疗组分别给予等同于临床剂量的相应药物,正常组和模型组给予生理盐水进行对照。通过检测血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)及肝组织中羟脯氨酸(Hyp)和观察肝组织病理切片来评价肝纤维化程度,检测血清中白细胞介素6(IL-6),乙酰胆碱酯酶(Ach E),高迁移率族蛋白1(HMGB1),内毒素(LPS)变化趋势。结果:与正常组比较,模型组大鼠血清ALT,AST,IL-6,Ach E,LPS,HMGB1水平及肝组织Hyp含量明显升高(P<0.01),模型组肝组织病变较为明显;与正常组比较模型组胶原面积显著增加;与模型组比较,治疗组明显降低大鼠血清中ALT,AST,IL-6,Ach E,LPS,HMGB1水平及肝组织Hyp含量(P<0.05),肝组织病变明显减轻,胶原面积明显降低;同时苦参素组与模型组比Ach E显著降低(P<0.05),联合用药与苦参素组比Ach E显著升高(P<0.05)。结论:甘草酸铵联合苦参素可抗由CCl_4诱导的大鼠肝纤维化,抗肝纤维化主要可能是通过减少大鼠体内LPS的含量和降低IL-6,HMGB1的表达来实现的,并且联合用药可改善临床上单独使用苦参素降低乙酰胆碱酯酶下降的情况。
OBJECTIVE: To study the inhibitory effect of glycyrrhizin combined with oxymatrine on hepatic fibrosis induced by carbon tetrachloride (CCl 4) in rats and its related mechanism. Methods: SD rats were randomly divided into 6 groups with 10 rats in each group, which were normal group, model group, colchicine positive group (2 mg · kg -1), glycyrrhizinate group (15 mg · kg -1) (30 mg · kg -1), ammonium glycyrrhizinate combined with matrine (15 mg · kg -1 +30 mg · kg -1) )) Group, except for the normal group, the other groups were used CCl_4 induced rat liver fibrosis model, the treatment group were given the equivalent of the corresponding clinical dose of drug, normal group and model group were given saline control. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver hydroxyproline (Hyp) and liver biopsy were evaluated to assess the degree of hepatic fibrosis. Serum (IL-6), acetylcholinesterase (Ach E), high mobility group box 1 (HMGB1) and endotoxin (LPS) were measured. Results: Compared with the normal group, the levels of ALT, AST, IL-6, Ach E, LPS and HMGB1 in the model group and the Hyp content in the liver tissue were significantly increased (P <0.01) Compared with the model group, the treatment group significantly reduced the level of ALT, AST, IL-6, Ach E, LPS, HMGB1 and the content of Hyp in the liver tissue of the model group (P <0.05) (P <0.05). The combined treatment and oxymatrine increased significantly (P <0.05) compared with Ach E group. CONCLUSION: Combining glycyrrhizin with matrine can inhibit CCl_4-induced hepatic fibrosis in rats, and anti-hepatic fibrosis may be mainly through decreasing the LPS content and decreasing the expression of IL-6 and HMGB1 in rats, and Combination therapy can improve the clinical use of oxymatrine alone reduce the decline of acetylcholinesterase.