钙通道阻滞剂对梗死心肌中不同部位心肌连接蛋白43表达的影响

Effect of calcium channel blocker on gap junctional connexin 43 in infarcted myocardium in rats

目的:研究L和L/T型钙通道阻制剂对梗死心脏不同部位(坏死区域、肥厚区域等)心肌组织中连接蛋白43(Cx43)的影响。方法:随机将大鼠48只分为假手术组、心肌梗死(MI)组、阿莫地平(L型钙通道阻滞剂)组和米贝拉地尔(L/T型钙通道阻滞剂)组(每组n=12只)。通过结扎大鼠左冠状动脉建立MI模型,术前7 d,上述4个组分别用安慰剂、L型钙通道阻滞剂阿莫地平4 mg/(kg.d)和L/T型钙通道阻滞剂米贝拉地尔10 mg/(kg.d)。术后1、3、7 d,分别检测左心室游离壁(LVFW,梗死区)、心室间隔(IS,肥厚区)和右心室壁(RV),正常心肌组织中Cx43蛋白的表达。术后7 d显微直视下测LVFW处MI病灶的大小、IS的厚度及左心室的大小。结果:IS中Cx43蛋白表达于术后1、3、7 d呈逐渐增加的趋势;LVFW中Cx43蛋白的表达于术后1、3、7 d时均处于低水平,与对照组相比差异显著(P<0.05)。RV中Cx43蛋白的表达于术后1、3、7 d无显著差异,与对照组相比也无显著性差异。米贝拉地尔能明显地抑制LVFW心肌组织中Cx43表达的下调,缩小MI病灶;阿莫地平则抑制肥厚心肌中Cx43蛋白的表达,明显抑制IS的肥厚。结论:MI病理过程中,梗死病灶内Cx43的表达下调,肥厚组织中Cx43的表达上调。L和L/T型钙通道阻滞剂均能减轻心肌重构与选择性地调节心肌组织中Cx43的表达有关。

AIM： To investigate the effect of cardiac L- and L/T-type Ca^＋ channels on gap junctional connexin 43 （Cx43） in myocardium infarcted heart remodeling of rats. METHODS： Rat myocardium infarction model was established by permanent ligation of the left coronary artepy. Infarcted rats were trea- ted with oral placebo, amlodipine [ L-channel blockade, 4 rag/（ kg · day） ] or mibefradil [ L/T-channel blockade, 10 mg/（kg· day] beginning 7 days before induction of myocardial infarction （MI）. Protein levels of Cx43 were measured 1, 3 and 7 days postcoronary occlusion in the noninfarcted and infarcted myocardium. Infarct size and left ventricular dilation were determined in picrosirius red-stained hearts. RESULTS： MI induced an upregulation of Cx43 protein in the hypertrophied interventricular septum （IS） （ maximmn 7 days postinfarction） , whereas Cx43 protein expression of Cx43 decreased markedly in the infarcted myocardinm of left ventricular free wall （LVFW） 1, 3 and 7 days postinfarction, with significant differences compared with those in control group （P 〈0. 01 ）. Carvedilol inhibited the protein upregulation of Cx43 and thickness of IS, decreased left ventricular dilation and reduced infarct size more obviously 7 days postinfarction. CONCLUSIONS： Infarction-induced cardiac hypertrophy is accompanied by upregulation of Cx43 in IS, whereas Cx43 is downregulated in LVFW in the process of cardiac infarcted pathogenesis. Cardiac L- and L/T-type Ca^2＋ channel blockade differentially reduced postinfarction remodeling, which is associated with the selective regulation of cardiac Cx43 in remodeling myoeardium.