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出 处:《北京中医药大学学报》2008年第7期448-451,I0003,共5页Journal of Beijing University of Traditional Chinese Medicine
基 金:国家重点基础研究发展计划(973计划)资助项目(No.2006CB504801);上海市重点学科建设资助项目(No.Y0302);上海市教育委员会E-研究院建设计划资助项目(No.E-03008)
摘 要:目的探讨虫草菌丝提取物(CME)对二甲基亚硝胺(DMN)肝纤维化大鼠肝窦内皮细胞(SECs)损伤和表型改变的影响。方法采用DMN复制大鼠肝纤维化模型,分别于3 d、2周、4周作为观察时相点;透射电镜观察肝组织超微结构,免疫组织化学法观察肝窦壁CD44、Ⅷ因子相关抗原(vWF);放射免疫法测定血清透明质酸(HA)含量。造模同时给予CME 0.74 g/kg灌胃,每日1次,共4周。结果DMN造模后第3天,CD44染色减弱、vWF阳性染色明显增强,SECs窗孔减少,血清HA含量显著升高(P<0.05),4周时可见SECs失窗孔和SECs下基底膜形成;CME早期(3 d)能够使SECs失窗孔减轻;CME灌胃2周、4周后,大鼠血清HA水平下降(P<0.05),肝窦壁CD44表达增强、vWF阳性染色减弱(P<0.05),SECs失窗孔和SECs下基底膜形成减轻。结论CME能够减轻DMN大鼠肝窦内皮细胞损伤和表型改变,抑制肝窦毛细血管化形成。Objective To study the effect of Cordyceps mycelia extract(CME) on injury and phenotype shift of liver sinusoidal endothelial cells(SECs) in rats with dimethylnitrosamine(DMN)-induced liver cirrhosis.Methods The rat liver fibrosis model was established by peritoneal injection of DMN(at a dose of 10 mg·kg^-1,3 times a week,for 4 wks).The dynamic changes of liver cirrhosis were observed at different time points(3 d,2 w,4 w).Liver ultrastructure was observed by electron microscope.The expressions of CD44 and von Willebrand factor(vWF) were examined by immunohistochemistry.The serum hyaluronic acid(HA) content was measured by radioimmunoassay.On the meantime CME were taken orally by 0.74 g·kg^-1·d^-1.Results The numbers of CD44 positive staining SECs in the 3 d model rats were obviously less than those of normal rats(P〈0.05);vWF positive staining increased;the numbers of fenestrae rapidly decreased,but serum HA content rapidly increased(P〈0.05).The defenestration and formation of basement membrane of SECs were observed in the 4 wk model rats.In the CME-treated 3 d and 2 wk rats,the defenestration and formation of basement membrane of SECs were alleviated.In the CME-treated 2 and 4 wk rats,serum HA content decreased(P〈0.05),CD44 expression increased,vWF positive staining decreased,the numbers of fenestrae increased,and formation of basement membrane decreased.Conclusions CME is able to decrease the injury and phenotype shift of SECs,inhibit the formation of capillarization in rats with the DMN-induced liver cirrhosis.
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