摘要
目的探讨基质金属蛋白酶-2/基质金属蛋白酶-2特异性组织抑制因子(MMP-2/TI MP-2)在脱氧皮质酮(DOCA)-盐型高血压大鼠(DHR)心脏微小血管重塑中的作用及其可能的调节机制。方法30只雄性SD大鼠,等分和制作为对照组、模型组、波生坦组、氨氯地平组和雷米普利组。5周末处死动物,检测心脏微小血管密度和MMP-2/TI MP-2蛋白与基因的表达。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/TI MP-2的蛋白表达上调;波生坦和氨氯地平能明显减轻微小血管损害,下调MMP-2/TI MP-2的mRNA和蛋白表达;雷米普利不能减轻微小血管损害,也不影响MMP-2/TI MP-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/TI MP-2表达可能参与微小血管病变的病理机制,内皮素-1和血压可能是通过调节MMP-2/TI MP-2表达参与微小血管病变。
Objective: To explore the role of MMP-2/TIMP-2 in the remodeling of cardiac microvasular of DOCA-salt hypertensive rats(DHR), and investigate the mechanism of it.Method: Thirty male Sprague-Dawley rats were unilaterally neprectomiled, and were divided into 5 groups including control, placebo, bosentan, amlodipine and ramipril group. They were plot to death after 5 weeks treatment. 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. Results: DOCA-salt hypertensive rats exhibited a marked decrease of microvascular density,and an increase of expression of MMP-2/TIMP-2. Amlodipine nearly normalized arterial pressure and suppressed all these changes. Bosentan had a very small effect on arterial pressure but decreased microvasular density and downregulated the expression of MMP-2/TIMP-2. Ramipril had no effect on arterial pressure,microvascular density and the expression of MMP-2/TIMP-2.Conclusion: Humoral factors such as endothelin may play a role besides high blood pressure in microvascular density in DOCA salt hypertension.MMP-2/TIMP-2 may play an important role in microvascular change.
出处
《微循环学杂志》
2005年第4期17-21,F0002,共6页
Chinese Journal of Microcirculation
