肢体远隔缺血后处理联合吗啡后处理增强对心肌缺血／再灌注损伤的保护作用

Combined morphine and limb remote ischemic postconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury

目的评估联合应用肢体远隔缺血后处理（remote ischemic postconditioning，RIP）和吗啡后处理能否获得增强的心肌保护作用。方法采用大鼠在体心肌缺血，再灌注损伤（ischemia／reperfusion injury，I／RI）模型，采用随机数字表法将60只大鼠分为6组（每组10只）：空白对照组（Sham组）、缺血／再灌注（ischemia／reperfusion，I／R）组（I／R组）、缺血预处理（ischemic preconditioning，IPC）组（IPC组）、肢体RIP组（RIP组）、吗啡后处理组（M组）以及联合应用肢体RIP和吗啡后处理组（M＋RIP组）。实验中连续监测心律失常情况，计算缺血期和再灌注早期的心律失常评分，检测血清肌酸激酶同工酶（ereatine kinase MB，CK-MB）和心脏肌钙蛋白I（cardiac troponin I，cTnI）浓度，并采用伊文蓝和氯化三苯基四氮唑（triphenyltetrazolium chloride，TYC）双重染色法测定心肌梗死面积。结果I／R组、IPC组、RIP组、M组和M＋RIP组的心肌梗死面积分别是（56．0±9．1）％、（23．9±5．5）％、（40．4±11．1）％、（47．7±9．3）％和（27．2±6．7）％。与I／R组比较，M＋RIP组再灌注早期心律失常发生率和心律失常评分、血清CK-MB和cTnI浓度以及心肌梗死面积均明显降低（P〈0．05）；这些参数在IPC组和M＋RIP组之间差异无统计学意义（P〉O．05）。结论在大鼠在体心肌I／RI模型，联合应用肢体RIP和吗啡后处理可获得增强的心肌保护作用，其心肌保护作用类似于IPC。

Objective To determine whether combined morphine and limb remote ischemic postconditioning could provide an enhanced protection against myocardial ischemia/reperfusion injury. Methods Using rat in vivo myocardio ischemia/reperfusion injury（I/RI） model, sixty male SD rats were allocated into six groups（n=10） by random number method： control group （group sham）, ischema/reperfusion（I/R） group（group I/R）, ischemic preconditioning group（group IPC）, remote ischemic postconditioning group（group RIP）, morphine postconditioning group （group M）, and combined morphine and remote ischemic postconditioning groups （group M＋ RIP）. Arrhythmias were monitored continuously during the experiment and scored in early I/R period. Serum creatine kinase MB （CK-MB） and cardiac troponin I（cTnI） levels were assayed. The infarction area was determined by Evans blue and triphenyltetrazolium chloride（TYC） staining method. Results The infarction area was （56.0±9.1）%, （23.9±5.5）%, （40.4±11.1）%, （47.7±9.3）% and （27.2±6.7）% in the I/R, IPC, RIP, M and M＋RIP groups, respectively. The infarction area, serum CK-MB, cTnI level, incidence and score of arrhythmias during early reperfusion period were significantly reduced in group M＋RIP compared to group I/R （P〈0.05）, butshowed no significant differences between IPC and M＋RIP groups （P〉0.05）. Conclusions This experiment demonstrates that combined morphine and limb remote ischemic postconditioning provides an enhanced protection against myocardial I/RI which is comparable to ischemic preconditioning.