【摘要】 目的:探讨维生素E(VitE)抗小鼠日本血吸虫病肝纤维化作用及其机制.方法:用日本血吸虫尾蚴皮肤敷贴法感染小鼠,构建日本血吸虫病肝纤维化模型,以肝纤维化达Ⅱ级或Ⅱ级以上作为开始VitE治疗标志.实验分5组:正常对照组、模型组及VitE高、中、低剂量组(每日150,50,5mg/kg),8wk末处死动物,HE和VG染色对肝组织进行病理学检查,分光光度法检测肝组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,免疫组化SP法检测肝星状细胞(HSC)标记物α-平滑肌动蛋白(α-SMA)表达,RT-PCR方法检测肝脏α1(I)型前胶原mRNA表达.结果:VitE降低模型组肝脏MDA含量[(5.00±0.31)μmol/gvs(11.66±1.84)μmol/g,P<0.05],提高SOD活性[(249.84±26.22)μkat/gvs(120.11±42.61)μkat/g,P<0.05];减少α-SMA阳性表达[(0.41±0.02)vs(0.68±0.02),P<0.05];降低肝脏胶原含量[(0.23±0.01)vs(0.60±0.11),P<0.05]和α1(I)型前胶原基因表达[(0.28±0.01)vs(0.85±0.15),P<0.05].结论:VitE具有抗小鼠日本血吸虫病肝纤维化作用,其机制与抗脂质过氧化作用、抑制HSC活化和增殖、降低α1(I)型前胶原基因表达和胶原合成有关.更多还原

【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 α-smooth muscle actin (α-SMA) 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 RT-PCR. RESULTS: Vit E reduced MDA content [(5.00±0.31) μmol/g vs (11.66±1.84) μmol/g, P<0.05] and increased SOD activity[(249.84±26.22) μkat/g vs (120.11±42.61) μkat/g, P<0.05] in the liver in model group in a dose- dependent manner. Besides, Vit E decreased the number of α-SMA positive cells [(0.41±0.02) vs (0.68±0.02), P<0.05] in a dose-dependent manner. Further, Vit E diminished the increased collagen content [(0.23±0.01) vs (0.60±0.11), P<0.05] and inhibited the increased α1 (I) procollagen mRNA expression [(0.28±0.01) vs (0.85±0.15), P<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 anti-lipid peroxidation, inhibition of HSC activation and proliferation, and reduction of α1(I) procollagen mRNA expression and collagen production by Vit E.更多还原