【作者】 杨灵捷；

【导师】 彭广能；

【作者基本信息】 四川农业大学 ， 临床兽医学， 2009， 硕士

【摘要】 目的:观察加味四逆散对实验性犬肝纤维化的预防效果和初步探索其机理,从而为该药临床应用提供较好的理论及实验依据。方法:选用24只健康成年杂交犬,体重10-15Kg,雌雄不限,常规免疫驱虫一个星期后开始实验。随机分为三组:模型组,中药组,西药组。动物自由采食与饮水,试验期为8周。采用皮下多点注射45%的CCl4菜籽油乳剂制作肝纤维化模型。中药组在给予CCl₄的同时口服加味四逆散浓缩煎剂。西药组在给予CCl₄的同时口服秋水仙碱。试验前后,每周从犬颈静脉采血,测定各组犬的红细胞总数、白细胞总数、血红蛋白、红细胞压积、红细胞平均体积、平均红细胞血红蛋白含量、平均红细胞血红蛋白浓度;测定各组犬的肝功能（TP、ALB、ALT、AST、TBIL、DBIL）、血清丙二醛（MDA）、过氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-px）、血清羟脯氨酸（Hyp）等指标的变化。试验结束时,处死全部实验动物,部分肝作肝匀浆处理,用于测肝组织匀浆羟脯氨酸（HyP）含量。结果:中药组犬的白细胞总数从试验开始到第三周一直呈升高的趋势,第四周下降,第五周反弹升高,从第六周开始逐渐降低。第三、四、五周时与造模前相比有显著差异（P＜0.05）,第六、七周时与造模前相比无显著差异（P＞0.05）;在第7周时,中药组与模型组的白蛋白含量相比较,存在极显著差异（P＜0.01）;在第7周时,中药组的直接胆红素与试验前不存在显著差异（P＞0.05）,而模型组的直接胆红素与试验前差异显著（P＜0.05）;从第2周起中药组血清ALT与模型组存在显著差异（P＜0.05）;从第4周起中药组血清AST显著低于模型组（P＜0.05）;从第2周起中药组SOD的含量较模型组均显著升高（P＜0.01或P＜0.05）,中药组GSH含量较模型组均显著升高（P＜0.01或P＜0.05）,中药组的MDA含量均显著低于模型组（P＜0.01或P＜0.05）;中药组犬血清中羟脯氨酸的含量也呈上升趋势,并从第2周开始一直显著高于试验前水平（P＜0.01）;实验结束时,模型组肝脏胶原含量也极显著高于中药组和西药组（P＜0.01）,中药组与西药组之间无显著差异（P＞0.05）。结论:加味四逆散抗犬肝纤维化机理与改善肝功能、提高机体抗氧化能力,抑制脂质过氧化以及抑制胶原合成,促进胶原蛋白降解,减少胶原沉积有关。抗炎效果强于秋水仙碱。在肝纤维化尚未完全形成之前,早期使用加味四逆散治疗,可以防止肝纤维化的形成,阻断肝纤维化的发展,达到逆转肝纤维化的目的。更多还原

【Abstract】 Objective: To study the effect of jiaweisinisan(JWSNS) on the prevention and its mechanism. Accordingly, it can offer preferably theoretics and experimentation thereunder for small animal clinic.Methods: 24 adult healthy hybrid dogs weighed about 10 -15kg were used as experimental animals, and were randomly divided into 3 groups,the model group,the Chinese herb group and the colchicines group. Hepatic fibrosis in dogs was induced by mixture of carbon tetrachloride and colza oil. the dogs of Chinese herb group and colchicines group were given JWSNS and colchicines respectively to observe the effects of JWSNS and colchicines on the formation of hepatic fibrosis. Before and after the test,the blood cell were counted and the serum levels of Total protein(TP),Albumin(ALB),Alanine aminotransferase(ALT), Aspartate aminotransferase(AST),Total bilirubin(TBIL),Direct bilirubin(DBIL),Ma!ondia-ldehyde(MDA),Superoxide dismutase(SOD), glutathione peroxidase(GSH-px), Hydroxyp-roline(HyP) were determined each week.Hydroxyproline(HyP) level in the liver was detected after the experiment.Reslut: The WBC of Chinese herb group had shown a rising trend from the start to the third week, declined in the fourth week ,a rebound increased in the fifth week,then came down in the sixth week. The WBC of Chinese herb group showed significant changes compare with the experiment start during the three,four,five weeks (P<0.05) .but it showed no significant difference compared with the experiment start during the six,seven weeks (P>0.05) . The serai levels of ALB of Chinese herb group showed significant changes compare with that of model group during the seven weeks (P<0.01) .The serm levels of DBIL of Chinese herb group showed no significant changes compared with the experiment start during the seven weeks (P>0.05 ),but that of model group showed significant changes compared with the experiment start during the seven weeks (P<0.05) . the serm levels of ALT of Chinese herb group showed significant difference compared with that of model group from the second week (P<0.05) . the serm levels of AST of Chinese herb group is significantly lower than that of model group from the fourth week (P<0.05) . the serum superoxid dismutase(SOD) and glutathione peroxidase(GSH-px) activity of Chinese herb group were significantly highter than that of model group,and the malondialdehyde(MDA) concentration was significantly lower than that of model group,the serum hydroxyproline concentration in Chinese herb group is significantly higher than that of model group(P<0.05) from the second week. At the end of the trial, the collagen content in liver tissues in Chinese herb group is significantly lower than that of model group (P<0.01) .Conclusion: It’s mechanism possibly has something with improve the canine liver function, enhance antioxidation, Inhibit peroxidation of lipid, Inhibit collagen synthesis, Promote collagen degradation and Slow progression of hepatic fibrosis. It has more powerful anti-inflammatory effect than that of colchicines. it is a availability prescription of prevent hepatic fibrosis.更多还原