卡维地洛对肾性高血压大鼠左室重构影响的实验研究  

Effect of carvedilol on left ventricular remodeling in renovascular hypertensive rat

作　　者：夏芳[1] 王晋明[1] 王芳[1] 梁远红[1] 严玲[1] 宋晓华[1] 

机构地区：[1]武汉大学人民医院心血管内科,430060

出　　处：《实用医学杂志》2005年第1期17-19,共3页The Journal of Practical Medicine

摘　　要：目的:观察第三代β受体阻滞剂卡维地洛防治肾性高血压大鼠左室重构的作用。方法:建立两肾一夹(2K1c)大鼠肾血管性高血压左室重构模型。术后8周随机分成3组:(1)假手术组(n=8);(2)2K1c组(n=8);(3)卡维地洛组(n=8)。治疗组直接灌胃给药。12周后行血流动力学分析,应用病理学方法评价整体心肌肥厚和组织胶原的表达,免疫组化方法检测MMP-2、TIMP-2的表达情况。结果:与假手术组相比,2K1c组大鼠术后发生明显左心室肥厚和纤维化,收缩压(SBP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室重量(LVM)、左室重量指数(LVMI)、胶原的含量及MMP-2、TIMP-2的表达显著高于健康的对照组(P<0.01),左室最大收缩和舒张速率(±dp/dtmax)均显著降低。卡维地洛能降低SBP、LVSP、LVEDP、LVM,而±dp/dtmax均显著升高;减少左室心肌中总体胶原中的合成及MMP-2、TIMP-2表达。结论:MMP-2、TIMP-2与左心室肥厚细胞外基质有关,卡维地洛能改善血流动力学和左室功能,有效地防止肾性高血压大鼠左室重构。Objective To observe the effect of the third generation β blocker carvedilol in preventive vertricular remodeling in renovascular hypertensive rat. Methods Animal models of two kidney one clip renovascular hypertensive (2K1c RHR)were made. Twenty four 2K1c RHR rats categorized into 3 groups randomly:(1)sham group;(2)2K1c group;(3)Carvedilol group. After 8 weeks of drug therapy by gavaga,the parameter of hemodynamics was determined, cardiac hypertrophy and extracellular matrix remodeling were evaluated by morphologica examination. Protein expression of matrix metalloproteinase (MMP 2), tissue inhibitor of metalloproteinase (TIMP 2)was examined by immunohistochemical analysis. Results Comparaed with sham operated group, 2K1c RHR induced hypertrophy and extracellular matrix remodeling predominantly occurred in the left ventricular and extracellular matrix remodeling were dominantly occurred in the left ventricular of collagen. SBP,LVSP, LVEDP, LVM, LVMI,MMP 2 and TIMP 2 were significant increased in 2K1c group, however, significant decreased could be seen in dp/dtmax and +dp/dtmax. After carvedilol treatment, incomparsion with 2K1c group, carvedilol significant decreased could been in SBP, LVSP, LVEDP and LVMI, while significant increased could be seen in +dp/dtmax. dp/dtmax. The interventricular septal thickness, total collagen, and the expression of MMP 2 and TIMP 2 were decreased. Conclusion MMP 2 and TIMP 2 are involved in the cardiac extracelluar matrix remodeling. Carvedilol can improve hemodynamic and LV function, prevent the left ventricular remodeling.

关 键 词：左室重构 大鼠 卡维地洛 TIMP-2 肾性高血压 MMP-2 表达 学分 结论 整体 

分 类 号：R541.3[医药卫生—心血管疾病]