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目的:研究内源性κ-阿片受体(κ-OR)的激动剂强啡肽在触发缺血后处理(postconditioning,Postcon)中的抗凋亡作用及潜在机制。方法:除了假手术组,SD大鼠(每组6只)制作缺血再灌注模型,进行了左冠状动脉前降支闭合30分钟后,再灌注2小时伴有或不伴有缺血后处理。在再灌注前5分钟静脉注射选择性κ-受体拮抗剂nor-binaltorphimine(nor-BNI)。氯化三苯四染色测定心肌梗死面积。用分光光度计测定血浆中肌酸激酶(CK)、乳酸脱氢酶(LDH)水平和心肌细胞凋亡蛋白酶-3(caspase-3)活性。TUNEL法检测心肌细胞凋亡。ELISA法检测血清和心肌中强啡肽含量。结果:缺血/再灌注(I/R组)组的梗死面积,caspase-3活性,细胞凋亡指数,CK和LDH活性等明显高于假手术组(P<0.01)。与I/R组相比,Postcon明显减少梗死面积,caspase-3活性,细胞凋亡指数,CK及LDH活性(P<0.01)。Postcon可使强啡肽含量显著增加(P<0.01)。除强啡肽含量外,上述所有的作用均被nor-BNI所阻断。结论:心脏保护和后处理的抗凋亡作用是通过激活κ-OR,至少部分通过增加强啡肽的水平来介导的。
AIM: To investigate the anti-apoptotic effect and possible mechanism of dynorphin, an agonist of endogenous κ-opioid receptor (κ-OR), in postconditioning (Postconditioning). Methods: Sprague-Dawley rats (6 rats in each group) were given ischemia-reperfusion model except for sham-operation group. The left anterior descending coronary artery was occluded for 30 minutes and reperfusion for 2 hours with or without ischemic postconditioning . The selective κ-receptor antagonist nor-binaltorphimine (nor-BNI) was injected intravenously 5 minutes before reperfusion. Determination of myocardial infarction size by trichloride chloride staining. The levels of creatine kinase (CK), lactate dehydrogenase (LDH) and the activity of caspase-3 in plasma were measured by spectrophotometer. TUNEL method was used to detect cardiomyocyte apoptosis. Enzyme linked immunosorbent assay was used to detect the content of dynorphin in serum and myocardium. Results: The infarct size, caspase-3 activity, apoptotic index, CK and LDH activity in I / R group were significantly higher than those in sham operation group (P <0.01). Compared with I / R group, Postcon significantly reduced infarct size, caspase-3 activity, apoptotic index, CK and LDH activity (P <0.01). Postcon increased the dynorphin content significantly (P <0.01). In addition to the dynorphin content, all the above effects were blocked by nor-BNI. Conclusion: The cardioprotective and post-treatment anti-apoptotic effects are mediated through the activation of κ-OR, at least in part, by increasing the level of dynorphin.