迷走神经刺激对大鼠缺血性心律失常的影响及其机制

目的:探讨急性心肌缺血时刺激迷走神经对室性心律失常的影响及其潜在的机制。方法:结扎大鼠冠状动脉前降支制备急性心肌缺血模型作为心肌缺血组(MI,n=25)、缺血+迷走神经刺激组(MI-VS,n=25)、缺血+迷走神经刺激+阿托品组(MI-VS-Atr,n=25)和假手术组(SO,n=20)。心电图监测室性心律失常的发生。Western blot分析缝隙连接蛋白43(Cx43)的磷酸化蛋白及总量表达变化。RT-PCR分析Cx43 mRNA的表达变化。免疫荧光观察Cx43表达分布情况。结果:MI-VS组室速/室颤发生率(16.0%,4/25)较MI组(52.0%,13/25)显著降低(P<0.05)。冠脉结扎30 min后,与SO组相比,MI组磷酸化Cx43的比例明显减少(P<0.05);迷走神经刺激明显抑制了缺血所致的Cx43脱磷酸化(P<0.05);而阿托品明显阻断了迷走神经刺激对磷酸化Cx43的保护作用。MI组Cx43 mRNA表达均较SO组显著减少(P<0.05);而MI-VS组Cx43 mRNA表达较MI组显著增加(P<0.05)。免疫荧光发现缺血能够诱导Cx43的分布发生改变,而迷走神经刺激能够抑制缺血引起的Cx43的分布改变。结论:急性心肌缺血时迷走神经刺激能够抑制室性心动过速或室颤的发生,其机制可能主要与迷走神经刺激抑制了Cx43的脱磷酸化及其分布变化有关。

Effects of Vagal Nerve Stimulation on Ischemia-Induced Ventricular Arrhythmias in Rats

Objective: To investigate the effect and the potential mechanism of vagal nerve stimulation on ventricular arrhythmias during acute myocardial ischemia in rats.Methods: Ninety five male rats were randomly assigned into four groups as myocardial ischemia(MI) group(n=25,ligation of the anterior descending coronary),myocardial ischemia vagal stimulation(MI-VS) group(n=25),myocardial ischemia vagal stimulation atropine(MI-VS-Atr) group(n=25) and sham operation(SO) group(n=20,without coronary ligation).Ventricular arrhythmias were monitored by an electrocardiogram.Western blot and RT-PCR were used for analyzing Connexin 43(Cx43) protein and Cx43 mRNA expression,respectively.Immunofluorescence analysis was used for observing the changes of Cx43 protein distribution.Results: Compared with that in the MI group,the incident of VT/VF in the MI-VS group decreased significantly(52.0% versus 16.0%,P<0.05) during the 30-minute ligation.After the 30-minute ligation,the percentage of the phosphorylated Cx43 of the MI group decreased markedly compared with that of the SO group(P<0.05).However,Cx43 dephosphorylation was significantly suppressed by vagal nerve stimulation while this effect was markedly inhibited by atropine(P<0.05).The Cx43 mRNA content of the MI group decreased significantly compared with that of the SO group(P<0.05),while the Cx43 mRNA content of the MI-VS group markedly increased compared with that in the MI group(P<0.05).Immunofluorescence confirmed that ischemia could induce the distribution changes of Cx43 while vagal nerve stimulation could prevent the changes of Cx43 distribution.Conclusion: Vagal nerve stimulation could inhibit ventricular arrhythmias by preserving Cx43 phosphorylation and prevent the changes of Cx43 distribution induced by ischemia during acute myocardial ischemia.