基质金属蛋白酶-2在高血压大鼠心脏中表达的意义及氨氯地平对其的影响

Signifance of expression of MMP-2/TIMP-2 and the effect of the intervention of amlodipine in DHR heart

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1周,随机等分为3组。对照组,饮自来水;另2组分别为模型组和氨氯地平组,开始每周予脱氧皮质酮50 mg.kg-1,ip,连续5周;氨氯地平组用氨氯地平30 mg.kg-1.d-1灌胃,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,分别行血浆内皮素-1(ET-1)浓度、微小血管密度及MMP-2/MMP-2特异性组织抑制因子(TIMP-2)蛋白和基因表达的检测,评价在氨氯地平干预下微小血管病变与MMP-2/TIMP-2表达间关系。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;氨氯地平能抑制血压升高,明显减轻微小血管损害,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,血压可能是通过调节MMP-2/TIMP-2表达参与微小血管病变;干预MMP-2/TIMP-2的表达可能为防治高血压靶器官损害的新的靶点。

Objective： To explore the role of MMP-2 in myocardial microvasular remodeling of DOCA sal hy perteasive rats （DHR）. Method： Thirty male Sprague-Dawley rats unilaterally neprectomiled, were randomly divided into 3 groups. One group served as a control, drinking tap water, two other groups were administered DOCA （50 mg·kg^- ·week^-1 ） subcutaneously, and fed with drinking water containing 1 %saline , simutaneously, given placebo, amlodipine （30 mg·kg^-1·d^-1）. After 5 weeks they were killed. 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 a saturated solution of KCl ）, were quickly removed and weighted. Arterioles （〈120 mm in lumen diameter） were identified in the myocardium by being immunolabelled 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 expressions of MMP-2/TIMP-2 protein were evaluated in the subendocardial myocardium of left ventricular. RT-PCR was used to measure the expression of mRNA of MMP-2/ TIMP-2. Result,DOCA-salt hypertensive rats exhibited a marked decrease of mierovascular density , and an increase of expression of MMP-2/TIMP-2. Amlodipine nearly normalized arterial pressure and suppressed all these changes . Conclusion ： High blood pressure may play a role in microvaseular density in DOCA salt hypertension ,MMP-2/TIMP-2.may play an important role in microvascular change. MMP-2/TIMP-2 activation may be a new potential target in heart protection.