【摘要】 目的探讨维生素E(VitE)对小鼠日本血吸虫性肝损害的保护作用及其机制。方法日本血吸虫尾蚴皮肤敷贴法感染小鼠构建日本血吸虫病模型,随机分5组:正常对照组、模型组及VitE高、中、低剂量组,感染尾蚴同时分别给予高、中、低剂量(150、50、5mg/kg)VitE,灌胃给药,每日1次共8周,8周末处死动物,HE、VG染色及透射电镜对肝组织进行病理学检查,应用分光光度法检测肝组织丙二醛(MDA)、羟脯氨酸(Hyp)含量和超氧化物歧化酶(SOD)活性,采用免疫组织化学SP法检测肝星状细胞(HSC)标记物α-平滑肌动蛋白(α-SMA)表达情况,并检测血浆丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平。结果VitE抑制模型组肝脏虫卵肉芽肿反应,减小肉芽肿直径(P<0.01),减轻炎性细胞浸润和肝细胞变性、坏死程度;降低ALT和AST水平(P<0.01);降低肝组织MDA含量(P<0.01),提高SOD活性(P<0.01);减少α-SMA阳性细胞数(P<0.01),均呈剂量效应关系。VitE对肝脏Hyp含量无明显影响(P>0.05)。结论VitE对小鼠日本血吸虫性肝损害具有保护作用,其机制与VitE抑制肝脏虫卵肉芽肿和炎症反应、抗脂质过氧化作用、抑制HSC活化和增殖及保护肝脏细胞免受自由基损害有关。更多还原

【Abstract】 Objective To investigate the protective effect of vitamin E(VitE) and its mechanisms in hepatic damage produced by Schistosoma japonicum infection in mice. Methods The mice were infected with cercariae of Schistosoma japonicum percutaneously. Each mouse was exposed to(20±1) cercariae. The mice were randomly divided into five groups: normal control group, model group,and intervention groups which were treated with three different doses of VitE via gastric infusion every day, including 150 mg/kg, 50 mg/kg and 5 mg/kg, as soon as the mice were infected. The mice were sacrificed at the end of the eighth week. Liver lesions were evaluated by HE, VG staining and transmission electron microscopy. Immunohistochemistry for α-smooth muscle actin(α-SMA) as an activated hepatic stellate cell(HSC) marker was performed to detect and quantify activated HSCs by SP technique. The contents of malondialdehyde (MDA) and hydroxyproline (Hyp)as well as the activity of superoxide dismutase(SOD) in liver tissue were determined by the spectrophotometric method. The serum alanine aminotransferase(ALT) and aspartate aminotransferase (AST) were detected. Results The hepatic granulomas formation surrounding deposited eggs was inhibited by VitE with minishing the diameter of granulomas(P<0.01), and the inflammatory cells infiltration and hepatocyte denaturation and necrosis were relieved, and the level of the serum ALT and AST(P<0.01) and the content of MDA(P<0.01) in the liver were reduced, and the activity of SOD(P<0.01) in the liver was increased in a dose-dependent manner. In addition, the numbers of α-SMA positive cells were decreased(P<0.01) in a dose-dependent manner. However, VitE had no effect on the content of Hyp in the liver(P>0.05). Conclusions VitE has protective effects on hepatic injury produced by Schistosoma japonicum infection in mice, and the protective mechanisms are associated with VitE alleviating hepatic granulomas and inflammatory response, opposing lipid peroxidation, inhibiting HSC activation and proliferation, and protecting hepatic cells against free radical damage.更多还原