丙泊酚预处理与缺血预处理保护大鼠体外心脏缺血再灌注损伤作用的比较

Comparison of effects of propofol pretreatment and ischemic preconditioning on ischemia-reperfusion injury in the isolated rat heart

目的:以缺血预处理(IPC)为标准观察丙泊酚预处理对大鼠体外心脏再灌注损伤的保护作用并探索其可能机制。方法:建立大鼠体外心脏Langendorff灌流模型并随机分为对照组(A组, n=8)、丙泊酚预处理组(B组,n=6)、IPC组(C组,n=6)及5 羟癸酸(5 HD)对照组(D组,n=8)、5 HD加丙泊酚预处理组(E组,n=6)、5 HD加 IPC组(F组,n=7)共6组。连续记录各组心脏血流动力学指标及冠状动脉流量变化,进行再灌注性心律失常评分,并计算心脏梗死面积。结果:B、C、E组血流动力学指标、冠状动脉流量、心律失常评分、梗死面积显著优于A组,以C组最显著(P<0.01或0.05),而D、F组与A组比较差异无统计学意义。结论:丙泊酚预处理与 IPC均可改善体外大鼠心脏再灌注所致的血流动力学紊乱、冠状动脉循环受损及再灌注性心律失常的发生,并缩小心脏梗死面积,但丙泊酚上述保护效应较 IPC弱。阻滞线粒体 KATP通道开放对丙泊酚预处理作用无影响,推测该通道与其保护效应无关。

Objective:To compare the effects of propofol pretreatment and ischemic preconditioning on ischemia-reperfusion injury in the isolated rat heart and to determine whether propofol shared the same mechanism of IPC, which is related to mitochondrial K ATP channels. Method: Male rat hearts were isolated and perfused with oxygenated Krebs-Hensleit (K-H) in a Langendorff apparatus, then randomly divided into 6 groups. All isolated hearts were subjected to 30 min of no-flow global ischemia followed by 120 min reperfusion, after a treatment period consisting of no intervention after the pretreatment without (group A, n=8) or with 5-HD(100 μmol/L, group D, n=8), 10 min propofol (50 μmol/L) followed by a 10-min washout period without (group B, n=6) or with 5-HD (100 μmol/L, group E, n=6), or two times of 5 min of ischemia followed by 5 min reperfusion after the pretreatment without (group C, n=6) or with 5-HD(100 μmol/L, group F, n=7).The hemodynamic index and coronary flow were monitored continuously, an arrhythmia score was used to quantify the arrhythmias during reperfusion and TTC staining was used to determine infarct size.Result:During reperfusion, compared with group A, hemodynamic values, coronary flow, arrhythmia score and infarct size were significantly improved in group B、C、E, especially in group C (P<0.01 or 0.05). Conclusion:Both propofol pretreatment and ischemic preconditioning improve function of the isolated rat heart after ischemia-reperfusion injury, attenuate the reperfusion arrhythmias and reduce infarct size. Propofol pretreatment shows less protection than ischemic preconditioning and is independent of mitochondrial K ATP channels.