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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,选择清热活血中药类方:鳖甲饮子、膈下逐瘀汤、复肝丸3首,以燮理枢机的燮枢汤作对照,观察比较不同类方对CCl4小鼠肝纤维化的药效作用。方法:10周龄C57BL/6小鼠雄性,体重(20±3)g,清洁级,随机分为正常组、模组型、鳖甲饮子组、膈下逐瘀汤组、复肝丸组、燮枢汤组。除正常组外,其他各组小鼠均以10%CCl4橄榄油溶液2 mL.kg-1体重腹腔注射,每周3次,共4周。造模同时,治疗组在造模之日起分别给予鳖甲饮子、膈下逐瘀汤、复肝丸、燮枢汤浸膏灌胃,每天1次,连续4周。正常组、模型组给予等体积的去离子水灌胃。试剂盒测定血清ALT,AST,γ-GT活性及Alb,TBil量,盐酸水解法观察肝组织羟脯氨酸(Hyp)含量,天狼猩红染色观察肝组织胶原沉积情况。结果:与正常组相比,模型组小鼠体重明显降低,肝体比、脾体比明显升高;肝细胞脂肪变性及炎性坏死明显。胶原纤维沉积明显,形成纤维间隔,并可见假小叶形成。血清ALT,AST,TBil,γ-GT均显著升高,肝组织Hyp含量明显升高。鳖甲饮子组AST有所降低,但肝细胞变性、炎症坏死和胶原沉积没有明显减少;膈下逐瘀汤组脾体比和γ-GT显著降低,肝细胞变性和炎症坏死有所减轻,胶原沉积有所减少;复肝丸组脾体比降低,AST,γ-GT显著降低,肝细胞变性和炎症坏死有所减轻,胶原沉积显著减少,Hyp含量明显降低;燮枢汤组脾体比降低,但炎症和纤维化程度未减轻。结论:复肝丸显示出较好的抗CCl4小鼠肝纤维化作用。
Objective: Based on the principle of square syndrome, through the screening of liver and kidney fibrosis screening database, select the traditional Chinese medicine prescriptions of clearing heat and activating blood: Biejia Yinzi, Gexia Zhuyu Decoction, Fugan Pill 3, Soup as a control, observed and compared different groups of CCl4 mice liver fibrosis effect. Methods: Male C57BL / 6 mice aged 10 weeks were divided into normal group, model group, Biejiayezi group, Gexia Zhuyu Decoction group and Fugan bolus group, weighing 20 ± 3g, , Xie Shu Tang group. In addition to the normal group, the other groups of mice were intraperitoneally injected with 2 mL.kg-1 body weight 10% CCl4 olive oil solution three times a week for 4 weeks. At the same time, the treatment group were given the turtle carambola, Gexiazhuyutang, Fugan Pill and Xieshe Tang extract orally respectively, once a day for 4 weeks. Normal group, model group given equal volume of deionized water gavage. The activity of ALT, AST, γ-GT and Alb, TBil in serum were measured by kit. The content of hydroxyproline (Hyp) in liver tissue was observed by hydrochloric acid hydrolysis method. The collagen deposition in hepatic tissue was observed by Sirius red staining. Results: Compared with the normal group, the body weight of the model group decreased significantly, and the ratio of liver to body and spleen increased significantly. The fatty degeneration and inflammatory necrosis of hepatocytes were obvious. Collagen fibers deposited significantly, forming a fiber space, and the formation of pseudolobules. Serum ALT, AST, TBil, γ-GT were significantly increased, liver Hyp content was significantly increased. The serum levels of AST in the turtle decoction group decreased, but the hepatocyte degeneration, inflammation, necrosis and collagen deposition did not decrease obviously. The ratio of spleen and γ-GT in the Gexiazhuyutang decoction group was significantly decreased, the degeneration of hepatic cells and inflammatory necrosis were alleviated, Collagen deposition decreased; Fugan decoction group decreased spleen, AST, γ-GT was significantly reduced, hepatocellular degeneration and inflammation and necrosis were reduced, collagen deposition was significantly reduced, Hyp content was significantly reduced; Decreased, but the degree of inflammation and fibrosis did not reduce. Conclusion: Fugan Pill shows better anti-CCl4 mouse liver fibrosis.