运动预处理后内源性阿片肽对大鼠心肌缺血再灌注损伤早期保护作用

Early Cardioprotection of Endogenous Opioid Peptides with Myocardial Ischemic Reperfusion Injury after Exercise Preconditioning

目的:探讨运动预处理后内源性阿片肽对大鼠心肌缺血再灌注损伤早期保护作用及机制。方法:健康雄性SD大鼠60只,随机分成假手术组(sham组)、缺血再灌注模型组(I/R组)、运动预处理组(EP组)和运动预处理+纳洛酮组(EPN组)。在运动预适应模型基础上,结扎左冠状动脉前降支复制大鼠心肌缺血再灌注模型,采用多道生理记录仪描记血流动力学参数,用酶联免疫法(ELISA)检测血清心肌肌钙蛋白I(cTnI)和血浆β-内啡肽(β-End)、强啡肽A(Dyn A)和亮氨酸-脑啡肽(L-Enk)含量,用原子分光光度法检测心肌中钙离子(Ca2+)浓度。结果:1与I/R组相比,EP组在再灌注期LVSP、±dp/dtmax降低幅度明显减小(P<0.05);与EP组相比,EPN组在再灌注60分钟后LVSP和-dp/dtmax值下降,且具有显著性差异(P<0.05)。2与I/R组相比,EP组血清cTnI漏出明显减少,具有显著性差异(P<0.05);EPN组血清cTnI降低,但差异不显著(P>0.05);与EP组相比,EPN组中血清cTnI值明显升高,有统计学意义(P<0.05)。3与I/R组相比,EP组和EPN组血浆中β-End、Dyn A、L-Enk浓度均明显升高,且有显著性差异(P<0.05);EP组与EPN组各项指标差异不显著(P>0.05)。4与I/R组相比,EP组心肌细胞胞浆中Ca2+浓度明显降低,具有显著性差异(P<0.05);EPN组心肌细胞胞浆中Ca2+浓度有降低趋势,但差异不显著(P>0.05);与EP组相比,EPN组中心肌细胞胞浆中Ca2+浓度明显升高,有统计学意义(P<0.05)。结论:运动预处理对心肌缺血再灌注损伤有保护作用,内源性阿片肽可能通过对抗交感神经兴奋和经阿片受体后途径维持细胞内钙稳态,保持细胞结构完整和功能正常,维持心脏舒缩功能,发挥早期的保护效应。

Objective： This article attempts to explore the early protective effect and mechanism of endogenous opioid peptides with myocardial ischemic reperfusion injury after exercise preconditioning. Methods： Sixty healthy male SD rats are randomly di- vided into sham group, I/R group, EP group, EPN group. After establishing of EP animal model, the rats are ligated ramus descendens anterior arteriae coronariae sinistrae to induce myocardial ischemic reperfusion. Then the parameter of hemodynamics are traced, and serum cardiac troponin I （cTnI）, ptasmaβ-End, Dyn A, L-Enk level is detected by euzymelinked immunosorbent assay （ELISA）, and myocardium Ca2＋ density is detected by atom absorption spectrophotometry. Results： （1） Compared with the group I/R, reduce range of LVSP, ±dp/dtmax decreases significantly in group EP during reperfusion phase （P〈0.05） ; Compared with the group EP, LVSP, !dp/dtmax decreases significantly in group EPN during reperfusion phase （P〈0. 05）. （2） Compared with the group I/R, the serum cTnI decreases significantly in group EP （P〈0.05）, the cTnl level in serum decreases without statistical significance in group EPN （P2〉0. 05） ; Compared with the group EP, the cTnl level in serum increases in group EPN. （3） Compared with the group I/R, the 13-End, Dyn A, L-Enk in plasma increases significantly in group EP- and EPN （P〈0. 05 or P〈0. 01）, there is no significant difference in group EP and EPN （P〉0. 05）. （4） Compared with the group I/R, the Ca2＋ level in cardiac muscle cell cytoplasm decreases significantly in group EP （P〈0.05）, the cardiac muscle cell cytoplasm Ca＋ decreases without statistical significance in group EPN （P〉0.05） ; Compared with the group EP, the Ca2 level in cardiac muscle cell cytoplasm increases significantly in group EPN （P〈0. 05）. Conclusion： EOP mitigates myocardial ischemic reperfusion injury significantly via maintaining intraeellular calcium homeostasis and counteracting sympathetic nerve ex- citation and activation of the opioid receptor may play a crucial role in EP.