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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。
AIM: To investigate the role of matrix metalloproteinase-2 (MMP-2) in microvascular remodeling and its possible regulation in deoxycorticosterone-salt hypertensive rats (DHR). Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups after one week of excision of the left kidney. Control group, drinking tap water; the other two groups were model group and amlodipine group, began weekly deoxycorticosterone 50 mg.kg-1, ip, for 5 weeks; amlodipine group with amlodipine 30 mg. kg-1.d-1 for 5 weeks. Animals were sacrificed at the end of the 5th week. Blood and heart samples were collected according to the corresponding requirements. Plasma concentrations of endothelin-1 (ET-1), microvessel density, and tissue inhibitor of metalloproteinase-2 / MMP-2 ) Protein and gene expression, evaluate the relationship between microvascular disease and the expression of MMP-2 / TIMP-2 under amlodipine intervention. Results: There was an increase in arteriolar density and a decrease in capillary density in the submandocardial myocardium of DHR. The mRNA expression of MMP-2 and MMP-2 / TIMP-2 were up-regulated. Amlodipine could inhibit the increase of blood pressure, Significantly reduce microvascular damage, down-regulate the mRNA and protein expression of MMP-2 / TIMP-2. There was a good correlation between MMP-2 expression and microvessel density. Conclusions: There are microangiopathy in the heart of DHR. The expression of MMP-2 / TIMP-2 may be involved in the pathogenesis of microangiopathy. The blood pressure may be involved in the microangiopathy by regulating the expression of MMP-2 / TIMP-2. / TIMP-2 expression may be a new target for the prevention and treatment of hypertension target organ damage.