【作者】 胡秀萍；

【导师】 杨雁； 明亮；

【作者基本信息】 安徽医科大学 ， 药理学， 2005， 硕士

【摘要】 本资料从以下三方面研究了复方黄芪提取物（compound astragalus extract,简称CAE）的抗肝纤维化作用及其作用机制: （1） CAE对CCl₄致大鼠慢性肝损伤及肝纤维化的保护作用 利用四氯化碳(12.5%CCl₄,4ml·kg^-1,sc,每周2次×13wk),诱导大鼠肝纤维化模型,观察了CAE对大鼠肝纤维化的影响。结果表明:CAE 3个剂量(60、120、240mg·kg^-1)均可明显降低CCl₄升高的肝与脾指数以及血清ALT与AST水平,还可明显降低所升高的血清A/G以及肝组织羟脯氨酸（HyP）含量和血清透明质酸（HA）含量,并且能升高所降低的肝组织超氧化物歧化酶（SOD）水平和降低所升高的肝组织MDA含量;CAE还能明显改善CCl₄致肝纤维化病理组织学变化。 （2） CAE对BDL诱导大鼠胆汁淤积性肝硬化的保护作用 采用胆总管结扎（bile duct ligation,BDL）诱导大鼠胆汁淤积性肝硬化模型,观察CAE对肝硬化的影响,实验结果表明:CAE 3个剂量组不仅能明显降低肝、脾指数、血浆ALT以及肝组织的HyP和MDA含量,同时使肝硬化大鼠的肝组织SOD活性和TP明显升高,而且可明显减少肝硬化大鼠的腹水量以及明显增加24小时尿钠、钾的排泄量,同时能明显降低四种不同切变率（1/200s、1/30s、1/5s、1/s）的全血粘度值和全血高切和低切相对粘度,低、高剂量还能明显降低血浆粘度（1/100s）,病理组织学结果显示,CAE 3个剂量均可使间质炎细胞浸润减少,CAE高剂量能明显减轻胆汁淤积性肝硬化大鼠的肝纤维化程度。 （3） CAE体外对免疫细胞的作用 CAE(1～90mg·L^-1)对亚适量ConA(2.5mg·L^-1)诱导T淋巴细胞增殖及分泌IL-2以及对亚适量LPS诱导B淋巴细胞增殖反应的量效曲线均呈钟罩型,提示其有浓度依赖性的双向免疫调节作用。 综上所述,CAE对CCl₄与BDL诱导的慢性肝损伤与肝纤维化均具有明显的保护作用,该疗效可能与其活血化瘀、抗炎、抗纤维化、抗氧化和免疫调节等更多还原

【Abstract】 The anti-hepatic fibrosis effects of compound astragalus extract （CAE） and its mechanismes of action were studied. The main contents are as follows:1. Effects of CAE on CCl₄- induced liver fibrosis in ratsThe liver fibrosis models were induced by CCU (12.5% CCl₄, 4 ml·kg^-1, sc, twice each week for 13 weeks) in rats to investigate the anti-hepatic fibrosis effect of CAE. The elevated indices of liver and spleen, and the elevated level of ALT, AST and HA in serum, and the elevated content of HyP and MDA in liver tissue induced by CCl₄ were significantly reduced by CAE treatment (60 、 120、 240 mg·kg^-1,ig,13 weeks). The depressed activity of liver SOD, the ratio of A/G and the body weight of rats were remarkably increased by CAE. The degrees of histopathology changes of liver in CCl₄- induced hepatic fibrosis rats were ameliorated remarkably by CAE treatment. These results showed that CAE has protective effects on CCl₄- induced liver fibrosis in rats .2. Effect of CAE on bile duct ligation （BDL）- induced cholestasis cirrhosis in ratsThe cholestasis cirrhosis models in rats were induced by BDL to investigate the effects of CAE on anti-hepatic fibrosis and improving blood circulation. The results showed that not only the elevated indices of liver and spleen, the elevated level of ALT in plasma, the content of HyP, MDA and ascites of rats were significantly reduced, but also the depressed activity of SOD of liver homogenates and the content of potassium and sodium excreted from urine for 24 hours were obviously increased by CAE treatment (60、 120、 240 mg·kg^-1). The elevated whole-blood viscosity under four kinds of shear rate （1/200s、 l/30s、 1/5s、1/s） and the elevated更多还原