当归补血汤不同配比组方的抗肝纤维化作用

目的：观察黄芪、当归不同配伍比例（5：1，1：1，1：5）的当归补血汤对大鼠肝纤维化的作用及其对肝脂质过氧化的作用特点。方法：将Wistar雄性大鼠随机分为正常组、模型组、芪归5：1方组、芪归1：1方组、芪归1：5方组及N-乙酰半胱氨酸对照组（NAC组）。以四氯化碳（CCl4）与高脂低蛋白饮食复合因素诱导大鼠肝纤维化模型，自造模之日起各药物组予灌胃6g／kg相应药物。干预6周后，观察肝组织炎症与脂肪变性及肝组织胶原沉积；测定血清肝功能指标，以及肝组织丙二醛（MDA）、羟脯氨酸（Hyp）含量、超氧化物歧化酶（SOD）和谷胱甘肽-S转移酶（GST）活性；Westem印迹法分析肝组织Ⅰ型胶原蛋白表达。结果：与正常大鼠比较，模型大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平与总胆红素（TBIL）含量明显升高，白蛋白（Alb）含量明显降低；肝组织脂肪变性与胶原沉积明显，GST活性增强，MDA含量增加，SOD活性降低。各中药配比组均能改善模型大鼠肝组织脂肪变性与胶原病理沉积，降低肝组织Hyp含量，提高血清Alb含量和SOD活性；其中芪归5：1方组较其他配比组的综合疗效较佳，在改善模型大鼠肝组织脂质过氧化损伤（MDA含量、SOD与GST活性）、抑制肝脏Ⅰ型胶原表达、改善血清肝功能（ALT水平与TBIL含量）等方面优于其他两种配伍比例组。结论：黄芪当归5：1，1：1，1：5不同配比的当归补血汤均有良好的抗实验性大鼠肝纤维化作用，但以黄芪当归5：1的经典配比方剂综合效果较好；其作用机制与抗肝脏脂质过氧化损伤有关。

Anti-hepatic Fibrosis Effect of "Danggui Buxue Decoction" with Different Proportions of Radix Astraga and Angelica Sinensis in Rats

Objective： To investigate the effects of ＂Danggui Buxue Decoction＂ with different proportions of Radix Astraga and angelica slnensis （5：1, 1：1, 1：5） on liver fibrosis and lipid peroxidation. Methods：The male Wistar rats were randomly divided into 6 groups： blank control group, model control group, ＂Danggui Buxue Decoction＂ with different proportions of Radix Astraga and angelica sinensis （5：1, 1：1, 1：5） groups and N-acetylcysteine（NAC） group. The model of liver fibrosis in rats was established with subcutaneous injection of carbon tetrachloride （CCl4） and high lipid and low protein diet. The rats of each group were administered with corresponding drug by garage at a dose of 6g/kg weight since the beginning of establishing model. Six weeks later, the inflammation, fatty degeneration and collagen deposition of liver were evaluated with HE staining and Sirius red staining; liver function, hepatic lipid peroxidation, namely, activity of superoxide dismutase （SOD） and content of GST and malon-diabdehyde （MDA） were tested with commercial kits; Hyp content in liver tissue was assayed with Jamall＇s method; and the protein expression of collagen I was detected by Western blot analysis. Results： Compared with the blank model group, in the model group the levels of ALT, AST and TBIL increased and the level of Alb decreased significantly; the activity of GST increased, the content of MDA increased and the activity of SOD decreased. There were also marked hepatic fatty degeneration and collagen accumulation in liver. In all the＂Danggui Buxue Decoction＂groups, the hepatic fatty degeneration and collagen accumulation were alleviated, the contents of liver Hyp decreased, the contents of Alb and the activity of SOD increased. While, among the ＂Danggui Buxue Decoction＂groups, the 5：1 proportion of Radix Astraga and angelica sinensis group is superior to the other two groups in alleviating the lipid peroxidation damage, inhibiting the protein expression of collagen and