| 王宪波,刘平,唐志鹏.虫草菌丝提取物抗二甲基亚硝胺诱致大鼠肝硬化肝窦毛细血管化作用机制的研究[J].,2009,(9):810-815 |
| 虫草菌丝提取物抗二甲基亚硝胺诱致大鼠肝硬化肝窦毛细血管化作用机制的研究 |
| Acting Mechanism of Cordyceps mycelia Extract for Antagonizing Hepatic Sinusoidal Capillarization in Rats with Dimethylnitrosamine Induced Liver Cirrhosis |
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| DOI： |
| 中文关键词: 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 |
| 英文关键词:dimethylnitrosamine rat matrix metalloproteinase-2 matrix metalloproteinase-9 Cordyceps mycelia extract hepatic sinusoidal capillarization liver sinusoidal endothelial cells |
| 基金项目:国家重点基础发展计划(973计划)基金资助项目(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) |
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| 中文摘要: |
| 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(ColⅣ),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ColⅣ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ColⅣ,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。 |
| 英文摘要: |
| Objective To study the acting mechanism of Cordyceps mycelia extract(CME) for antagonizing hepatic sinusoidal capillarization(HSC) in rats with dimethylnitrosamine(DMN) induced liver cirrhosis.Methods Rat liver cirrhosis model was established by peritoneal injection of DMN 10 mg/kg 3 times a week for 4 weeks.To rats in the CME-prevented group CME were administrated at a dose of 10 mL/kg,once a day,for 4 weeks.The observation time points were scheduled on the 3rd day(d3),and at the end of the 2nd(W2) and 4th week(W4) after modeling,and the following items were observed: hepatic ultrastructure was observed under electron microscope;expressions of CD44,von Willebrand factor(vWF) and typeⅣ collagen(Col Ⅳ) in the liver sinusoidal walls by immunohistochemistry;matrix metalloproteinase-2 and-9(MMP-2,MMP-9) activity under zymogram method;and serum hyaluronic acid(HA) content by radioimmunoassay.Results Observation at d3 showed MMP-2 and MMP-9 activity significantly increased,Col Ⅳ deposition and CD44 positive staining decreased,vWF positive staining increased in the liver sinusoidal walls,the fenestrae in the sinusoidal endothelial cells(SECs) decreased,and serum HA content increased(P<0.05);at W4,SECs defenestration and sub-SECs basal membrane formation were shown.In the CME-prevented group MMP-2 and MMP-9 activity significantly decreased(P<0.05);defenestration and basal membrane formation alleviated in the early stage(d3,W4);and at W2 and W4 decreases of HA content and vWF positive staining were shown,with increase of CD44 positive staining(P<0.05),more SECs fenestrae,and alleviated basal membrane formation.Conclusions The elevation of MMP-2 and MMP-9 activity in the early stage,which degrades the Col Ⅳ normally distributed under the sinusoidal endothelium,is an important factor for HSC formation.CME could inhibit the initiation of HSC by decreasing MMP-2 and MMP-9 activity in the early stage,and prevent its formation by decreasing SECs injury and phenotypic changes. |
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