迷走神经对快速起搏犬上腔静脉肌袖缝隙连接蛋白40,43重构的影响

目的研究迷走神经对犬上腔静脉(SVC)肌袖缝隙连接蛋白40(Cx40)、43(Cx43)重构的影响。方法24只杂种犬,随机等分为3组:假手术组(Sham组)、切除上腔静脉-主动脉根部(SVC-AO)脂肪垫组(RM组)和保留SVC-AO脂肪垫组(RS组)。RM组和RS组植入起搏器,500～650次/分起搏6W;Sham组保留SVC-AO脂肪垫植入起搏器但不起搏。以程序刺激或猝发刺激诱发心房颤动(AF),取SVC肌袖组织行Cx40、Cx43免疫组化染色并半定量分析,透射电镜观察缝隙连接(GJ)的超微结构。结果RS组有5只犬诱发出持续性AF(5/7),而Sham组和RM组无1只犬能诱发持续性AF。RM组和RS组的Cx40、Cx43蛋白表达均显著高于Sham组(P<0.05);RS组的Cx40、Cx43蛋白表达显著高于RM组(P<0.05)。Sham组和RM组的Cx40、Cx43端/侧比值均显著高于RS组(P<0.05)。与RM组比较,RS组GJ通道变短且宽,出现肌溶解及线粒体空泡状改变。结论迷走神经可能通过介导SVC肌袖Cx40、Cx43重构而使AF易于发生和维持;切除犬SVC-AO脂肪垫可减弱此效应。

Effects of vagus nerve on remodeling of connexin40, 43 in superior vena cava myosleeve in canine after rapid atrial pacing

Objective To investigate the effects of cardiac vagus nerves on remodeling of connexirAO, 43 in superior vena cava（SVC） myosleeve in canine. Methods Twenty four hybrid dogs were divided into sham operation group（Sham group,n = 8） ,SVC-aortic root （AO） fat pad removed group（RM group,n =8） and SVC-AO fat pad reserved group（RS group,n =8）. In RM group and RS group, right atrial pacing was performed at a frequency of 500 -650 bpm for 6 weeks to establish atrial fibrillatiou（AF） model. AF was induced by programmed stimulation or burst stimulation of atrial pacing. The expression and distribution of connexin 40（ Cx40）, 43 （Cx43） in the SVC myosleeve tissue in three groups were analyzed by immunohistochemical staining. Transmission electron microscope was used to observe the uhrastructural organization of gap junction （GJ）. Results Sustained AF could be induced in five of seven dogs（ 〉 15minutes） in RS group, but none of dogs had induced sustained AF in Sham group and RM group. The levels of Cx40, Cx43 in the SVC myosleeve in RM group and RS group were significantly higher than that in Sham group. Furthermore, the levels of Cx40, Cx43 in RS group were obviously higher than that in RM group. The ratio of end-to-end to side-to-side in RS group was lower than that in Sham group and RM group. Compared with RM group, the channel of GJ became shorter and wider in RS group. Sarcomere was dissolved and mitochondrion showed vacuole degeneration in RS group. Conclusions The remodeling of Cx40, Cx43 in SVC myosleeve tissue may be mediated by vagus nerves. It is conducive to the maintenance and stability of AF. However, this effect can be weakened by removing SVC-AO fat pad of canine.