钙通道阻滞剂对缺血心肌基质金属蛋白酶和纤连蛋白的影响  

The effect of calcium channel blockade on matrix metalloproteinases and fibronectin in the rat myocardial remodeling

作　　者：杨永健[1] 邓晶晶[2] 张鑫[1] 杨大春[1] 

机构地区：[1]成都军区总医院心血管内科 [2]成都医学院药学系,四川成都610083

出　　处：《中国药理学通报》2006年第8期987-991,共5页Chinese Pharmacological Bulletin

摘　　要：目的研究L和L/T型钙通道阻滞剂对梗死心肌基质金属蛋白酶(MMP2,3,9)及细胞外基质纤连蛋白(fibronectin,FN)的作用。方法结扎大鼠左冠状动脉建立心肌梗死模型,术前7d分别用安慰剂、L型钙通道阻滞剂阿莫地平(4mg·kg-1·d-1)、L/T型钙通道阻滞剂米贝拉地尔(10mg·kg-1·d-1)。术后1、3、7d分别检测左心室游离壁(LVFW)、室间隔(IS),右室壁(LV)基质金属蛋白酶2,3,9(MMP2,3,9)蛋白表达;免疫荧光检测LVFW、IS、RV心肌FN的分布。结果术后7dRV心肌排列基本正常,IS心肌肥厚,LVFW心肌有不同程度的坏死、肥厚及纤维化。术后1、3、7dISMMP2,3,9蛋白表达呈逐渐增加的趋势,同时FN表达逐渐减少,各时相点与假手术组相比差异有显著性(P<0.01);术后1、3、7dLVFWMMP2,3,9蛋白表达一直处于高水平,FN蛋白表达处于低水平,各时相点与假手术组相比差异有显著性(P<0.01)。米贝拉地尔更明显地抑制LVFWMMP2,3,9上调减少FN降解,缩小心肌梗死病灶。阿莫地平则抑制MMP2,3,9上调减少FN降解,明显抑制室间隔肥厚。结论心肌梗死病理过程中,梗死病灶内及肥厚组织中MMP2,3,9上调、FN降解,L和L/T型钙通道阻滞剂能减轻心肌重构与选择性的抑制心肌组织中的MMP2,3,9及FN降解有关。Aim To investigate the contribution of cardiac L-and L/T-type Ca^2＋ channels blockers on matrix metalloproteinases （MMPs） protein expression and fibronectin （FN） degradation following myocardial infarction（ MI ）. Methods Rat MI model was established by permanent ligation of left coronary artery. Infarcted rats were orally treated with placebo, amlodipine （ L-channel blocker, 4mg·kg^-1·d^-1 ） or mibefradil （L/T-Channel blocker, 10mg·kg^-1·d^-1） for 7 days before induction of myocardial infarction. Protein levels of MMP-2,3,9 and FN distribution were assayed by immunoflorescence at 1,3, 7 days post coronary occlusion in left ventricular free wall （LVFW） and myocardium interventricular septum （IS）. Results Pathological changes of myocardial tissues in IS and LVFW showed typical myocardial remodeling. The hypertrophy was dominant in IS, but in LVFW the characteristics including disordered alignament, hypertrophy of the myocytes, the discontinuity, dissolving of carediomyofibrills, and the hyperplasia of interstitial tissue were found 7 days after MI. The protein levels of MMP-2,3,9 increased in IS 1,3,7 days post MI gradually, whereas the protein levels of FN decreased gradually, the protein levels of MMP-2,3,9 increased significantly in LVFW 7 days post MI, and the protein levels of FN decreased significantly compared to control group, respectively（ P 〈 0. 01 ）. Amlodipine inhibited protein up-regulation of MMP-2, 3,9, decreased FN degagation and interventricular septal thickness. Mibefradil attenuated protein up-regulation of MMP-2,3,9, decreased FN degradation 7 days post infarction in LVFW and reduced infarct size more obviously. Condusions Infarction-induced cardiac hypertrophied tissue IS and infarcted myocardium LVFW was accompanied by an up-regulation of MMP-2,3,9, and degradation of FN. The effect of cardiac L and L/T-type Ca^2＋ channel blockers differentially reducing post infarction remodeling is associated with their selective inhibition of MMP-2,3,9 protein expr

关 键 词：钙通道 心肌重构 基质金属蛋白酶 纤连蛋白 

分 类 号：R-332[医药卫生] R322.11