特异性抑制内向整流性钾电流对缺血再灌注心脏的保护作用

Specific inhibition of inward rectifier potassium current protects the heart after ischemia/reperfusion

摘要:

目的 探究转基因特异性抑制心脏内向整流性钾电流(IK1)的小鼠在缺血预适应中对缺血心脏的保护作用。方法 选取IK1基因抑制小鼠分为2组:阳性表达者为观察组,阴性表达者为对照组。监测各组小鼠心律失常发生情况,采用离体心脏,观察缺血预适应对心脏缺血再灌注后心肌梗死面积、凋亡的影响。采用Western blot检测相关信号蛋白的表达。采用SPSS 17.0软件进行统计学分析,样本间比较采用t检验。结果 与对照组相比,观察组心律失常评分分值[(3.50±0.67) vs(7.42±0.70)分]、心肌梗死面积/左室面积的比值[(0.25±0.04)% vs(0.38±0.02)%]和心肌细胞凋亡指数[(202±93)‰ vs(822.5±97.5)‰]均显著降低(P<0.05)。Western blotting结果表明,与对照组相比,观察组磷酸化糖原合成酶激酶3[(1.41±0.16) vs(0.77±0.05)]和AKT[(1.84±0.20) vs(0.81±0.14)]及p-AKT[(1.87±0.27) vs(1.08±0.22)]均显著上调。结论 Kir2.1转基因抑制可减少缺血预适应后再灌注心肌梗死中心律失常的发生、心肌细胞的凋亡及心肌梗死面积,其机制可能部分与再灌注损伤补救激酶信号通路有关。

Abstract:

Objective To investigate the protective effects of the specific inhibition of inward rectifier potassium current (IK1) on the ischemic heart in a transgenic mouse model with ischemic preconditioning (IPC). Methods Mice with genetic inhibition of IK1 were divided into 2 groups:observation group with positive expression and control group with negative expression. Arrhythmia was monitored in each group. With the isolated heart, the effects were observed of IPC on the myocardial infarct size and apoptosis following ischemia/reperfusion (IR). Western blot was employed to detect the expressed proteins. SPSS statistics 17.0 was used for statistical analysis, and t-test for comparison between groups. Results Compared with the control group, the observation group had significantly lower arrhythmia score [(3.50±0.67) vs (7.42±0.70)scores], ratio of myocardial infarct size to left ventricular area [(0.25±0.04)% vs (0.38±0.02) %] and cardiomyocyte apoptosis index [(202±93) ‰ vs (822.5±97.5) ‰, P<0.05]. Western blotting revealed significantly greater up-regulation in the observation group than in the control group of phosphorylated glycogen synthase kinase 3 [(1.41±0.16) vs (0.77±0.05)], AKT [(1.84±0.20) vs (0.81±0.14)], and p-AKT [(1.87±0.27) vs (1.08±0.22)]. Conclusion Transgenic inhibition of Kir2.1 can potentially reduce the occurrence of arrhythmia, myocardial cell apoptosis, and myocardial infarct size in myocardial infarction following IPC, and its mechanism may be partially related to the Reperfusion Injury Salvage Kinases (RISK) pathway.