高洪燕 白殊同 刘金坤 喻晓雯 冯婧 黄祎

中圖分类号 R285.5 文献标志码 A 文章编号 1001-0408（2018）12-1625-04

DOI 10.6039/j.issn.1001-0408.2018.12.10

摘 要 目的：研究柔肝宝颗粒对肝纤维化模型大鼠相关指标的改善作用，为该制剂的进一步研发提供实验依据。方法：取雄性SD大鼠45只，按随机数字表法分为正常组、模型组、阳性对照组（扶正化瘀胶囊，给药剂量为0.4 g/kg）与柔肝宝颗粒高、低剂量组（给药剂量按生药计分别为16.8、8.4 g/kg），每组9只。除正常组外，其余各组大鼠皮下注射四氧化碳并给予高脂饲料和15%乙醇溶液喂养12周，以建立肝纤维化模型。造模完成后，给药组大鼠分别灌胃给予相应药物，每天1次，连续给药12周；正常组、模型组大鼠灌胃给予相应体积的水。采用倒置显微镜观察大鼠肝组织病理学变化；采用酶联免疫吸附测定法检测大鼠血清中肝功能指标[丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、白蛋白（ALB）]和肝纤维化指标[透明质酸（HA）、Ⅳ型胶原（Ⅳ-C）、 层粘连蛋白（LN）、Ⅲ型胶原前体（Ⅲ-PC）]的水平。结果：与模型组比较，柔肝宝颗粒高、低剂量组大鼠肝组织细胞空泡变性现象和纤维化程度均明显改善，中央静脉清晰可见，均未见扩张与萎缩，以高剂量组效果更为显著；血清ALT、AST水平均显著降低，ALB水平均显著升高（P<0.05或P<0.01）；其保肝作用与阳性对照药物相当，但在升高ALB方面效果较阳性对照药物更显著（P<0.05或P<0.01）；血清HA、Ⅳ-C、LN、Ⅲ-PC水平均有不同程度的下降，以高剂量组效果更为显著（P<0.05或P<0.01），其延缓肝纤维化进展的作用与阳性对照药物相当。结论：柔肝宝颗粒具有改善模型大鼠肝功能、延缓肝纤维化进展的作用。

关键词 柔肝宝颗粒；肝功能；肝纤维化；大鼠

ABSTRACT OBJECTIVE： To study the improvement effects of Rouganbao granules on liver fibrosis of model rats， and to provide experimental evidence for further development of this preparation. METHODS： Totally 45 male SD rats were divided into normal group， model group， positive control group （Fuzheng huayu capsules， 0.4 g/kg） and Rouganbao granules high-dose and low-dose groups （16.8， 8.4 g/kg by crude drug） according to random number table， with 9 rats in each group. Except for normal group， other groups were given CCl4 subcutaneously and high lipid diet+15% ethanol solution for 12 weeks to establish liver fibrosis model. After modeling， medication groups were given relevant medicine intragastrically， once a day， for consecutive 12 weeks. Normal group and model group were given corresponding volume of water intragastrically. The pathology change of liver tissues of rats was observed by inverted microscope. The levels of liver function indexes （ALT， AST， ALB） and liver fibrosis indexes （HA， Ⅳ-C， LN， Ⅲ-PC） were determined by ELISA. RESULTS： Compared with model group， liver cell vacuolation and liver fibrosis of rats were improved significantly in Rouganbao granule high-dose and low-dose groups； central vein was clearly visible， and no dilation and atrophy were found， especially in high-dose group； the serum levels of ALT and AST were decreased significantly， while the level of ALB was increased significantly （P<0.05 or P<0.01）， of which the protective effect for liver was similar to positive control drug but better in increasing ALB （P<0.05 or P<0.01）； the serum levels of HA， Ⅳ-C， LN and Ⅲ-PC were all decreased in varying degree， especially in high-dose group （P<0.05 or P<0.01）， of which the effect of relieving liver fibrosis was similar to positive control drug. CONCLUSIONS： Rouganbao granules can improve liver function and delay the progression of liver fibrosis in model rats.

KEYWORDS Rouganbao granules； Liver function； Liver fibrosis； Rat

肝纤维化是由于各种慢性肝病引起的持续或反复的肝实质炎症坏死破坏了肝脏纤维增生和分解的平衡，从而导致肝内纤维结缔组织过度沉积而形成的[1]。肝纤维化在临床表现为肝脏内纤维结缔组织异常增生，是一个动态过程，如不及时阻断或逆转，最终会导致肝硬化甚至肝癌，是我国人群的主要死亡原因之一[1-2]。……