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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 investigate the effects of Cordyceps mycelia extract (CME) on the damage and phenotypic changes of sinusoidal endothelial cells (SECs) in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Methods DMN was used to replicate rat liver fibrosis model. The 3rd, 2nd, and 4th weeks were used as observation time points. Ultrastructure of liver tissue was observed by transmission electron microscopy. CD44 and VIII factors related antigens were observed by immunohistochemical method. (vWF); Radioimmunoassay for the determination of serum HA. At the same time, the model was given CME 0.74 g/kg gavage once a day for 4 weeks. Results On the 3rd day after DMN was established, CD44 staining was weakened, vWF positive staining was significantly increased, SECs window was decreased, serum HA content was significantly increased (P<0.05), ESCs lost fenestration and basement membrane formation under SECs was seen at 4 weeks. Early CME (3 days) reduced the loss of SECs; after 2 weeks or 4 weeks of CME administration, serum HA levels decreased (P<0.05), CD44 expression in liver sinusoidal wall increased, and vWF positive staining decreased. <0.05), loss of SECs and formation of basement membrane under SECs. Conclusion CME can reduce the damage and phenotypic changes of liver sinusoidal endothelial cells in DMN rats and inhibit the formation of hepatic sinusoidal capillaries.