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目的:基于方证相对原理,通过肝肾纤维化方证数据库筛选分析,选择膈下逐瘀汤、复肝丸、燮枢汤、鳖甲丸4首方剂,观察他们对二甲基亚硝胺(DMN)大鼠肝纤维化的药效作用。方法:大鼠随机分为正常组、模型组、膈下逐瘀汤组、复肝丸组、燮枢汤组、鳖甲丸组和N-乙酰半胱氨酸对照药组。除正常组外,各组大鼠均以DMN 10μg/kg腹腔注射,每天1次,每周连续3天,共4周。造模第3周开始给予相应药物灌胃:膈下逐瘀汤7.03g/kg、复肝丸6.43g/kg、燮枢汤12.51g/kg、鳖甲丸5.40g/kg,正常组与模型组给予等体积的生理盐水灌胃,每天1次,连续4周。试剂盒测定血清ALT、AST、γ-GT活性及Alb、T.Bil含量,盐酸水解法测定肝组织羟脯氨酸(Hyp)含量,HE染色与天狼猩红染色观察肝组织炎症与胶原沉积情况。结果:与正常组比较,模型组大鼠体重明显降低,脾体比升高,腹水形成;血清ALT、AST、Tbil及肝组织Hyp含量明显升高,血清Alb明显降低;肝组织病理染色可见大量炎性细胞浸润、胶原纤维沉积明显,纤维间隔、部分假小叶形成。与模型组比较,复肝丸组、N-乙酰半胱氨酸组脾体比和ALT、Hyp含量等显著降低,肝细胞变性和炎症坏死明显减轻,胶原沉积明显减少,AST、Tbil、γ-GT无明显变化;膈下逐瘀汤组脾体比、ALT、Hyp含量等降低,但死亡率较高,肝组织病理炎症及纤维化程度均较重;燮枢汤组脾体比降低,其余指标无明显变化;鳖甲丸组脾体比降低,ALT、Hyp含量有所降低,但肝细胞变性、炎症坏死和胶原沉积无明显变化;结论:与N-乙酰半胱氨酸相似,复肝丸有较好的抗DMN大鼠肝纤维化作用。
Objective: Based on the principle of square syndrome, through the screening and analysis of the database of liver and kidney fibrosis, select four prescriptions of Gexiazhuyu Decoction, Fugan Pill, XieShuToup and BieJia Wan and observe their effects on dimethylnitrosamine (DMN) on hepatic fibrosis in rats. Methods: The rats were randomly divided into normal group, model group, Gexiazhuyutang group, Fugan pill group, Xieba soup group, Biejiawan group and N-acetylcysteine control group. Except the normal group, rats in each group were injected intraperitoneally with DMN 10μg / kg once daily for 3 consecutive days for 4 weeks. The rats in the normal control group and model group were given gavage of Zuxu Zhuyu Decoction 7.03g / kg, Fugan Pill 6.43g / kg, Xiexiao Decoction 12.51g / kg and Biejia Pill 5.40g / kg, Group given equal volume of saline gavage once a day for 4 weeks. Serum levels of ALT, AST, γ-GT, Alb and T.Bil were measured by kit, and hydroxyproline (Hyp) content in liver tissue was determined by hydrochloric acid hydrolysis. Liver inflammation and collagen deposition were observed by HE staining and Sirius red staining . Results: Compared with the normal group, the body weight of the model group decreased significantly, the ratio of spleen increased and the formation of ascites; serum ALT, AST, Tbil and liver tissue Hyp content increased significantly, serum Alb significantly decreased; Inflammatory cell infiltration, collagen deposition was obvious, the fiber interval, the formation of some false lobules. Compared with the model group, the spleen body ratio, ALT and Hyp contents in Fugan pill group and N-acetylcysteine group were significantly decreased, liver cell degeneration and inflammation and necrosis were significantly reduced, collagen deposition was significantly reduced, AST, Tbil, γ- GT did not change significantly; Gexiazhuyu Decoction group spleen ratio, ALT, Hyp content decreased, but the higher mortality, pathological inflammation and fibrosis of liver tissue were heavier; There was no significant change in the index; the ratio of spleen of Biema pill group was decreased, ALT, Hyp content was decreased, but the hepatocyte degeneration, inflammation, necrosis and collagen deposition had no obvious change; Conclusion: Similar to N-acetylcysteine, Pill has better anti-DMN rat liver fibrosis.