【摘要】 目的探讨基质金属蛋白酶-2(MMP-2)在脱氧皮质酮-盐型高血压大鼠(DHR)心脏微小血管重塑中作用及其可能的调节机制。方法30只雄性SD大鼠,切除左侧肾脏后一周,随机等分为3组。其中,一组为对照组,饮自来水;另两组分别为模型组和波生坦组,开始予脱氧皮质酮(DOCA)(50mg.kg-1.week-1)皮下注射,连续5周。5周末处死动物,按相应的要求留取血液和心脏标本,分别行血浆ET-1浓度、微小血管密度及MMP-2/TIMP-2蛋白和基因表达的检测。结果在DHR左心室心内膜下心肌中存在微小动脉密度增加和毛细血管密度减少,MMP-2的mRNA和MMP-2/TIMP-2的蛋白表达上调;波生坦能抑制血压升高,减轻微小血管损害,下调MMP-2/TIMP-2的mRNA和蛋白表达,MMP-2的表达同微小血管密度间具有良好的相关性。结论在DHR心脏中存在微小血管病变,MMP-2/TIMP-2表达可能参与微小血管病变的病理机制,内皮素-1可能是通过调节MMP-2/TIMP-2表达参与微小血管病变。更多还原

【Abstract】 Objective This study was performed to observe the effect of microvascular density,and the expression of MMP-2/TIMP-2 in the subendocardial myocardium of DOCA-salt Hypertensive Rats（DHR） left ventricle under the intervention of bosentan,and to evaluate the signifance of expression of MMP-2/TIMP-2 and the role of endothelin-1 on the expression of MMP-2/TIMP-2 in DHR heart.Methods Thirty male Sprague-Dawley rats were unilaterally neprectomiled,the 30 survived rats were divided into 3 groups according to random desigen.One group served as controls,drinking tap water,two other groups were administered DOCA(50mg·kg^-1·week^-1) subcutaneously,and fed with drinking water containing 1% saline,simutaneously,given placebo,bosentan,(100mg·kg^-1·d^-1),each for 5 weeks before they were plot to death.The systolic arterial pressure was monitored in all rats every week by measurement using a tail-cuff.The hearts,arrested in diastole（intravenous injection of asaturated solution of KCL）,were quickly removed,weighted.Arterioles（<20μm in lumen diameter） were identified in the myocardium by use of immunolabelling with an anti-smooth muscle α-actin antibody,and capillaries with an anti-laminin antibody with nuclear counterstaining and combined with computed morphometry,the arteriolar and capillary density,and the expression of MMP-2/TIMP-2 protein were employed to evaluate in the subendocardial myocardium of the left ventricular tissue.RT-PCR was used to measure the expression of mRNA of MMP-2/TIMP-2 with β-actin used as internal contras.Results DOCA-salt hypertensive rats exhibited a marked decrease of microvascular density,and an increase of expression of MMP-2/TIMP-2.Bosentan had a very small effect on arterial pressure but decreased microvascular density and downregulated the expression of MMP-2/TIMP-2.Conclusion Endothelin may play a role inmicrovascular density in DOCA-salt hypertension,MMP-2/TIMP-2 may play an important role in microvascular change.更多还原