远端缺血后处理对兔心脏缺血/再灌注损伤的保护作用及其机制研究

Protective Effect and its Mechanism for Remote Ischemic Post-conditioning in Myocardial Ischemia/reperfusion Injury in Experimental Rabbits

目的:观察远端肢体缺血后处理对兔心脏缺血/再灌注损伤的作用,并探讨其可能机制。方法:36只健康新西兰大白兔随机分为6组(每组6只):假手术组、缺血对照组、缺血后处理组(MPostC组)、远端肢体缺血后处理组(RPostC组)、缺血后处理+5-羟葵酸组(MPostC+5-HD组)、远端肢体缺血后处理+5-羟葵酸组(RPostC+5-HD)。结扎左冠状动脉左室支45 min,再灌注120 min造模,结扎双侧髂外动脉5 min骨骼肌短暂缺血。于缺血前、后及再灌注1 h、2 h观察心功能指标和肌酸激酶(CK)、乳酸脱氢酶(LDH)活力及心肌梗死范围。结果(:1)再灌注1 h、2 h后,MPostC组、RPostC组心功能指标较缺血对照组明显改善(P<0.05)。MPostC+5-HD组、RPostC+5-HD组分别较MPostC组、RPostC组改善不明显(P<0.05)(;2)再灌注2 h时,MPostC组、RPostC组的CK、LDH活力均显著低于缺血对照组(P均<0.05),MPostC+5-HD组、RPostC+5-HD组的CK、LDH活力分别较MPostC组、RPostC组明显增高(P均<0.05)(;3)缺血对照组的缺血范围[缺血区重量/左心室重量(AAR/LVg),缺血区面积/左心室面积(AAR/LVs)]与其他5组比较差异均无统计学意义(P>0.05);MPostC组、RPostC组梗死范围[梗死区重量/缺血区重量(AN/AARg)、梗死区面积/缺血区面积(AN/AARs)]均较缺血对照组明显降低(P均<0.05),MPostC+5-HD组、RPostC+5-HD组分别与MPostC组、RPostC组比,梗死范围均增加(P均<0.05)。MPostC+5-HD组、RPostC+5-HD组、缺血对照组的梗死范围组间差异无统计学意义(P>0.05)。结论:经典的缺血后处理和远端肢体缺血后处理对心脏缺血/再灌注损伤均有明显的保护作用,其共同的机制可能为线粒体ATP敏感钾通道(MitoKATP)的激活。

Objective： To observe the protective effect of ischemic post-conditioning on myocardial reperfusion injury with the potential mechanism in experimental rabbits. Methods： A total of 36 healthy New Zealand rabbits were divided into 6 groups： ① Sham group, ② Ischemic reperfusion control（CON） group,③ Myocardial ischemic post-conditioning（Mpost C） group, ④ Remote ischemic post-conditioning（RPostC） group, ⑤ MPostC ＋5-HD group, ⑥ RPostC ＋5-HD group. n=6 in each group. The ischemic reperfusion injury model was established by left ventricular descending artery occlusion for 45 min followed by reperfusion for 120 min. Bilateral external iliac artery was occluded for 5 min to induce the short skeletal muscle ischemia. The indexes of cardiac function and plasma CK, LDH activities were measured at baseline, end of ischemia and 1, 2 h after reperfusion respectively, the sizes of myocardial infarction（MI） were examined and compared among different groups. Results： ① Compared with CON group, the indexes of cardiac function were improved in MPostC and RPostC groups at 1, 2 h after reperfusion, P〈0.05, and compared with MPostC group and RPostC group, the indexes of cardiac function were improved in MPostC ＋5-HD and RPostC ＋5-HD groups, P〈0.05. ② Compared with CON group, plasma CK, LDH activitieswere decreased in MPost C and RPost C groups at 2 h after reperfusion, P〈0.05, and compared with MPost C group and RPostC group, the CK, LDH activities were increased in MPostC ＋5-HD and RPostC ＋5-HD groups, P〈0.05. ③ The ischemic ranges and areas were similar between CON group and the other 5 groups P〉0.05. The MI ranges and areas in MPostC and RPostC groups were much less than that in CON group, P〈0.05, and compared with MPostC group and RPostC group, the MI ranges and areas increased in MPostC ＋5-HD and RPostC ＋5-HD groups, P〈0.05. The MI ranges and areas were similar between CON group and MPostC ＋5-HD, RPostC ＋5-HD groups, P〉0.05. Conclusion： Classical ischemic post-conditioning and remote organ ischemic post-conditioning both have protective effect on myocardial reperfusion injury in experimental rabbit, which might be related to the activation of mitochondrial ATPsensitive potassium channels.