摘要
目的:研究L和L/T型钙通道对梗死心肌基质金属蛋白酶(MMP-2、MMP-3、MMP-9)及细胞外间基质肌腱蛋白(tenascin-c,TN-C)的影响。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1d、3d、7d分别检测左心室游离壁(left ventricular free wall,LVFW)MMP-2、MMP-3及MMP-9蛋白表达;免疫荧光检测LVFW心肌TN-C的分布。结果:术前LVFW心肌排列基本正常,术后7dLVFW心肌有不同程度的坏死、肥厚及纤维化。术后1d、3d、7dLVFWMMP-2、MMP-3、MMP-9及TN-C蛋白表达一直处于高水平,各时相点与基础值相比差异有显著性(P<0.01)。米贝拉地尔更明显地抑制LVFWMMP-2、MMP-3、MMP-9及TN-C上调,缩小心肌梗死病灶,阿莫地平能抑制MMP-2、MMP-3、MMP-9及TN-C上调,但较米贝拉地尔弱。结论:心肌梗死病理过程中,梗死病灶内MMP-2、MMP-3、MMP-9及TN-C上调,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MMP-2、MMP-3、MMP-9及TN-C表达有关。
Objective： To investigate the contribution of cardiac L-and L/T-type Ca^2＋ channels on matrix metalloproteinases（MMPs） protein expression and tenascin-c （TN-C）degradation mediated myocardial damage following myocardial infarction（MI）. Method： Rat MI model was established by permanent ligation of left coronary artery, infarcted rats were orally treated with placebo, amlodipine （L-channel blockade, 4mg.kg^-1.d^-1） or mibefradil （L/T-Channel blockade, 10 mg.kg^-1.d^-1） beginning 7 days before induction of myocardial infarction. Protein levels of MMP-2, MMP-3, MMP-9 and TN-C distribution also assayed by immunoflorescence. 1,3,7 days post coronary occlusion in left ventrlcular free wall （LVFW）. Result： Pathological changes of myocardial tissues in LVFW showed typical myocardial remodeling. The characteristics in LVFW included disordered alignament, hypertrophy of the myocytes, the discontinuity, dissolving of cardiomyofibrills, and the hyperplasia of interstitial tissue found 7 days after MI. The protein levels of MMP-2, MMP-3, MMP-9 increased in LVFW 1,3,7 days post MI, whereas the protein levels of TN-C increased also, there was a big difference from control （P 〈 0.01）. Amlodipine inhibited protein up-regulation of MMP-2, MMP-3, MMP-9 and TN-C, mibefradil attenuated protein up-regulation of MMP-2, MMP-3, MMP-9 and TN-C 7 days post infarction in LVFW, reduced infarct size more obviously. Conclusion：Infarcted myocardium LVFW was accompanied by an up-regulation of MMP-2, MMP-3, MMP-9, and TN-C. Cardiac L and L/T-type Ca^2＋ channel blockade differentially reduce post infarction remodeling associated with selective inhibition protein expression of MMP-2, MMP-3, MMP-9 and TN-C, respectively.
出处
《心肺血管病杂志》
CAS
2007年第3期170-173,共4页
Journal of Cardiovascular and Pulmonary Diseases
关键词
钙通道
心肌重构
基质金属蛋白酶
肌腱蛋白
动物实验
大鼠
Calcium channel
Myocardial remodeling
Matrix metalloproteinases
Tenascin-c
Animals labroratory, mus
