甘草酸铵联合苦参素抗大鼠肝纤维化作用及初步机制探讨

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(P0.01),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(P0.05),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(P0.05),联合用药与苦参素组比Ach E显著升高(P0.05)。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。

Anti-hepatic Fibrosis Effect of Ammonium Glycyrrhetate Combined Oxymatrine and Its Mechanism

Objective: To research the anti-hepatic fibrosis effect of ammonium glycyrrhetate combined oxymatrine in hepatic fibrosis rat induced by CCl₄ and its mechanism. Method: SD rats were randomly divided into six groups, namely normal group, model group, colchicine positive group (2 mg·kg^-1), ammonium glycyrrhetate group (15 mg·kg^-1), oxymatrine group (30 mg·kg^-1),ammonium glycyrrhetate combined oxymatrine group (15 mg·kg^-1+30 mg·kg^-1), with 10 in each group. Except for normal group, in the remaining groups, the rat liver fibrosis model were induced by CCl₄.Normal group and model group were given the saline, treatment groups were administered with the corresponding drugs of equal clinical doses. Their liver fibrosis were assessed by detecting serum alanine transaminase (ALT), aspertate aminotransferase (AST) and liver hydroxyproline (Hyp) and observing liver tissue pathology biopsy. Besides, serum interleukin-6(IL-6), acetylcholin esterase (AchE), high mobility group protein 1 (HMGB1), and lipopolysaccharide (LPS) were also detected. Result: Compared with model group,model group showed remarkable increases in ALT, AST, IL-6, AchE, LPS, HMGB1 and liver Hyp (P<0.01), significant liver tissue pathological changes, and notable expansion in collagen area. Compared with model group, ALT, AST and IL-6, AchE,LPS, HMGB1 levels and liver Hyp significantly decreased in treatment group (P<0.05), At the same time, compared with model group, oxymatrine group showed obvious decrease in the expression of AchE (P<0.05), and combination group showed a higher AchE expressions than oxymatrine group (P<0.05), and significant alleviation in liver tissue pathological changes and collagen area. Conclusion: Ammonium glycyrrhetate combined oxymatrine can inhibit CCl₄-induced liver fibrosis in rats by reducing the levels of LPS and the expression of IL-6, HMGB1.The combined administration can improve the clinical effect in declining acetyl cholinesterase by using oxymatrine alone.