维生素E对小鼠日本血吸虫病肝纤维化治疗作用及其机制.doc

维生素E对小鼠日本血吸虫病肝纤维化治疗作用及其机制 　 作者：牛丽文，杨镇，肖亮，张爱龙，李岽健，乌剑利 【关键词】 ,血吸虫病,日本；肝硬化；维生素E；氧化性应激；肝星状细胞；胶原I型 【Abstract】 AIM: To investigate the therapeutic effect of vitamin E(Vit E) and its mechanisms on liver fibrosis induced by Schistosoma japonicum infection in mice. METHODS: Mice were infected with Schistosoma japonicum cercariae percutaneously, and were divided into 5 groups: normal control group, model group, and intervention groups which were treated with three different doses of Vit E, 150, 50, and 5 mg/kg. That live fibrosis reached gradeⅡ or above was considered to be a marker of therapeutic start. The mice were killed at the end of the 8th week. Liver lesions were evaluated using HE and VG staining. Immunohistochemistry for αsmooth muscle actin (αSMA) as an activated hepatic stellate cell(HSC) marker was performed to detect and quantify activated HSC by SP technique. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in liver tissue were determined by spectrophotometric method. The α1(I) procollagen mRNA expression was measured by RTPCR. RESULTS: Vit E reduced MDA content ［(5.00±0.31) μmol/g vs (11.66±1.84) μmol/g, Plt;0.05］ and increased SOD activity［(249.84±26.22) μkat/g vs (120.11±42.61) μkat/g, Plt;0.05］ in the liver in model group in a dosedependent manner. Besides, Vit E decreased the number of αSMA positive cells ［(0.41±0.02) vs (0.68±0.02), Plt;0.05］ in a dosedependent manner. Further, Vit E diminished the increased collagen content ［(0.23±0.01) vs (0.60±0.11), Plt;0.05］ and inhibited the increased α1 (I) procollagen mRNA expression ［(0.28±0.01) vs (0.85±0.15), Plt;0.05］ in the liver in model group. CONCLUSION: Vit E has evident therapeutic effects on liver fibrosis resulted from Schistosoma japonicum infection in mice, and the mechanisms are associated with antilipid peroxidation, inhibition of HSC activation and proliferation, and reduction of α1(I) procollagen mRNA expression and collagen production by Vit E. 【Keywords】 Schistosomia