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Acting Mechanism of Cordyceps mycelia Extract for Antagonizing Hepatic Sinusoidal Capillarization in Rats with Dimethylnitrosamine Induced Liver Cirrhosis
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- Author:
- No author available
- Issue:
- 9
- DOI:
- 10.3321/j.issn:1003-5370.2009.09.011
- Key Word:
- 二甲基亚硝胺;大鼠;基质金属蛋白酶2、9;虫草菌丝;肝窦毛细血管化;肝窦内皮细胞
Abstract： 目的 探讨虫草菌丝提取物(CME)对二甲基亚硝胺(DMN)诱致大鼠肝硬化肝窦毛细血管化作用的机制.方法 将63只大鼠分为3组:正常组(18只)、模型组(30只)、用药组(15只,予CME).采用DMN 10 mg/kg腹腔注射, 每周连续3天,每天1次,共4周制作大鼠肝纤维化模型,分别于造模后3天、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)、Ⅳ型胶原(Col Ⅳ),酶谱法测定基质金属蛋白酶-2(MMP-2)和MMP-9活性;放射免疫法测定血清透明质酸(HA)含量.结果 DMN造模后3 天MMP-2、MMP-9活性显著增加,肝窦壁Col Ⅳ沉积显著减少、CD44 染色减弱、vWF阳性染色明显增强,肝窦内皮(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天,2 周时)能够显著降低MMP-2、MMP-9活性(P<0.05),SECs失窗孔和SECs下基底膜形成减轻;CME灌胃2、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窗孔增多,SECs基底膜形成减轻.结论 早期MMP-9、MMP-2活性升高,降解肝窦内皮细胞下正常分布的Col Ⅳ,是肝窦毛细血管化形成的重要因素;CME早期通过降低MMP-2、MMP-9活性,抑制肝窦毛细血管化的启动;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.
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