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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。

英文摘要:

Objective: To investigate the mechanism of dynorphin, an endogenous kappa opioid receptor (κ-OR) agonist in postconditioning (Postcon). Methods: Sprague Dawley (SD) rats (n=6) underwent a 30-min left anterior descending occlusion followed by 2h of reperfusion with or without a Postcon stimulus. The selective κ-OR antagonist nor-binaltorphimine (Nor-BNI) was administered i.v. 5 min before reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. Blood plasma of creatine kinase (CK) and lactate dehydrogenase (LDH) and myocardial caspase-3 activity were analyzed by spectrophotometrically. Myocardial apoptosis was analyzed by detection of TUNEL. Immunoreactive dynorphin in blood serum and myocardium was measured by an antigen-competitive ELISA. Results: Infarction size, caspase-3 activity, apoptotic index, CK and LDH were significantly higher in ischemic/reperfusion (I/R) group than that in vehicle group (P<0.01). Postcon reduced infarction size, caspase-3 activity, apoptotic index, CK and LDH (P<0.01 vs. I/R). Dynorphin content significantly increased after Postcon (P<0.01). All indexes described above were abolished by Nor-BNI, with the exception of dynorphin content. Conclusion: Cardiac protection and anti-apoptotic effect of Postcon is mediated by activation ofκ-OR. Effect of Postcon is mediated, at least partially, by enhanced dynorphin expression.

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