Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury
Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury
复制标题
DOI：
10.1016/j.lfs.2006.03.033
复制
发表时间：
2006-08-22
期刊：
影响因子：
6.1
通讯作者：
Yeh, Jwu-Lai
中科院分区：
文献类型：
--
作者：
Liang, Jhy-Chong;Chen, Hen-Rong;Yeh, Jwu-Lai
本实验观察了具有α/β肾上腺素受体阻滞活性的二氢吡啶类钙通道阻滞剂拉贝地洛尔-A对大鼠心肌缺血/再灌注（45 min/120 min）后心肌梗死范围、细胞凋亡和坏死的影响。在左冠状动脉闭塞前10分钟，用溶剂或拉地匹洛尔-A（0.25或0.5 mg/kg，静脉注射）处理大鼠。在溶剂组中，心肌缺血-再灌注诱导肌酸激酶（CK）释放，并引起心肌细胞凋亡，如DNA梯形形成和末端dUTP脱氧核苷酸转移酶缺口末端标记（TUNEL）染色所证明的。与赋形剂组相比，用拉贝地洛尔-A（0.25或0.5mg/kg）治疗显著减小了梗死面积（18.75 +/- 0.65%和8.27 +/- 0.29%对41.72 +/-0.73%，P < 0.01）。降低血清CK、CK-MB、乳酸脱氢酶（LDH）和肌钙蛋白T水平。此外，拉地匹地洛尔-A（0.5 mg/kg）使TUNEL阳性细胞从19.21 +/- 0.52%显著降低至9.73 +/- 0.81%（P < 0.01），这与拉地匹地洛尔-A组中DNA梯状条带的缺失一致。此外，拉贝地洛尔-A预处理还可降低缺血-再灌注心肌组织钙含量。总之，这些结果表明，labedipindielol-A，通过减少钙超载和细胞凋亡，在心肌缺血-再灌注过程中发挥抗梗死作用，并将在临床上用于预防急性心肌梗死。(c)2006爱思唯尔公司All rights reserved.
The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with alpha-/beta-adrenoceptor blocking activities, on myocardial infarct size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45 min/120 min) were investigated. Ten minutes prior to left coronary artery occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.5 mg/kg, i.v.). In the vehicle group, myocardial ischemia-reperfusion induced creatine kinase (CK) release and caused cardiomyocyte apoptosis, as evidenced by DNA ladder formation and terminal dUTP deoxynucleotidyltransferase nick end-labeling (TUNEL) staining. Treatment with labedipinedilol-A (0.25 or 0.5 mg/kg) reduced infarct size significantly compared to vehicle group (18.75 +/- 0.65% and 8.27 +/- 0.29% vs. 41.72 +/- 0.73%, P < 0.01). Labedipinedilol-A also reduced the CK, CK-MB, lactate dehydrogenase (LDH) and troponin T levels in blood. In addition, labedipinedilol-A (0.5 mg/kg) significantly decreased TUNEL positive cells from 19.21 +/- 0.52% to 9.73 +/- 0.81% (P < 0.01), which is consistent with absence of DNA ladders in the labedipinedilol-A group. Moreover, labedipinedilol-A pretreatment also decreased calcium content in ischemic-reperfused myocardial tissue. In conclusion, these results demonstrate that labedipindielol-A, through reduction of calcium overload and apoptosis, exerts anti-infarct effect during myocardial ischemia-reperfusion and would be useful clinically in the prevention of acute myocardial infarction. (c) 2006 Elsevier Inc. All rights reserved.