金属蛋白酶组织抑制剂1在抗纤复方Ⅰ号防治酒精性肝病中的作用

Role of Chinese medicine Kangxian Fufang I in the prevention and treatment of alcoholic liver disease and dynamic changes of tissue inhibitor of metalloproteinase-1 in rats

目的:研究抗纤复方Ⅰ号对酒精性肝病大鼠的预防及治疗作用及金属蛋白酶组织抑制剂1(TIMP-1)的动态变化及表达。方法:用灌胃的方法制备大鼠酒精性肝病的动物模型;在大鼠灌胃4,8,12,16周分别麻醉处死大鼠,留取标本进行HE染色、Masson胶原染色,应用免疫组织化学技术、免疫电镜技术及流式细胞术检测TIMP-1的动态变化和表达。结果:抗纤复方Ⅰ号预防及治疗组的肝组织胶原含量明显低于酒精性肝病组(P<0.05),TIMP-1水平也低于酒精性肝病组(P<0.05)。免疫组化可见酒精肝病组TIMP-1主要位于血管内皮细胞、窦内皮细胞及肝窦细胞的胞浆。结论:抗纤复方Ⅰ号可以有效地预防及治疗酒精性肝病,其机制可能与抑制TIMP-1的表达有关。

Objective： To investigate the role of Kangxian Fufang Ⅰ （KX Ⅰ）, a Chinese medicine,in the prevention and treatment of alcoholic liver disease and the dynamic changes of tissue inhibitor of metalloproteinase-1 （TIMP-1） in rats. Methods： The Wistar rat models of alcoholic liver disease were established by gastric lavage of alcohol. Eighty male Wistar rots were randomly divided into 4 groups： normal control group,alcoholic liver disease group,KX Ⅰ prevention group,and KX Ⅰ treatment group. At the end of weeks 4,8,12,and 16 after gastric lavage,5 rats from each group were killed,and the livers were removed for HE staining and Masson staining. The expression of TIMP-1 was detected by immunohistochemical method, immuno-electron microscopy, and flow cytometry. Results： Compared with alcoholic liver disease group,the content of liver collagen and the level of TIMP-1 were lower in KX Ⅰ prevention group and KX Ⅰ treatment group （P 〈 0.05）. In alcoholic liver disease group, TIMP-1 was mainly located in the cytoplasm of endothelial cells of hepatic artery and portal vein, sinusoidal endothelial cells, and sinusoidal cells. Conclusion： KX Ⅰ could effectively inhibit or inverse the course of alcoholic liver disease, which may be correlated with the expression of TIMP-1.