内源性κ-阿片肽介导的缺血后处理心肌保护作用  

Endogenous Kopioid Peptide Mediated Ischemic Postconditioning for Cardioprotectiong

作　　者：武敏[1] 郭海涛[2] 时全星[2] 李娟[2] 师建国[1] 裴建明[2] 

机构地区：[1]第四军医大学基础部病理学教研室,陕西西安710032 [2]第四军医大学基础部生理学教研室,陕西西安710032

出　　处：《现代生物医学进展》2011年第20期3809-3815,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金(30971060;30900535);国家重大新药项目基金(2009ZX09301-009-BD10)

摘　　要：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。Objective： To investigate the mechanism of dynorphin, an endogenous kappa opioid receptor （K -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 K -OR antagonist nor-binaltorphimine （Nor-BNI） was administered Lv. 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 of K -OR. Effect of Postcon is mediated, at least partially, by enhanced dynorphin expression.

关 键 词：后处理 凋亡 心脏 Κ-阿片受体 强啡肽 

分 类 号：Q95-33[生物学—动物学]