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

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。

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

AIM:To investigate the effect of cardiac L- and L/T-type Ca2+ 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 artery. Infarcted rats were treated with oral placebo, amlodipine ［L-channel blockade, 4 mg/(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) (maximum 7 days postinfarction), whereas Cx43 protein expression of Cx43 decreased markedly in the infarcted myocardium 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 Ca2+ channel blockade differentially reduced postinfarction remodeling, which is associated with the selective regulation of cardiac Cx43 in remodeling myocardium.