Department of Cardiology, Renmin Hospital of Gansu Province, Lanzhou, P.R. China.
Tohoku J Exp Med. 2011 Sep;225(1):51-7. doi: 10.1620/tjem.225.51.
Electrical remodeling at infarct border zone has been shown to contribute to the occurrence of ventricular arrhythmias after myocardial infarction (MI). Electrical remodeling is causally associated with sympathetic neural remodeling in MI. Semaphorin 3A (Sema3A), a potent neural chemorepellent for sympathetic axons, has been demonstrated to suppress sympathetic neural remodeling after MI. In the present study, we investigated whether treatment with Sema3A can ameliorate electrical remodeling at infarct border zones using a rat model of MI. Wistar rats underwent sham operation (n = 20), the ligation of left coronary artery (MI group, n = 30), MI with control adenovirus (Ad group, n = 30), and MI with Sema3A adenovirus (Sema3A group, n = 30). Eight weeks after treatment, electrophysiological properties including heart rate variability (HRV), monophasic action potential duration (MAPD) and effective refractory period (ERP) and the expression of arrhythmia-related ion channel proteins including Kv4.2, KChIP2 and Kir2.1 at the infarcted border of the left ventricle were examined. These channel proteins may be required for maintaining normal heart rhythm. Compared with the Ad group, Sema3A significantly increased HRV and shortened MAPD and ERP (all p < 0.05). The expression levels of Kv4.2, KChIP2 and Kir2.1 proteins were significantly decreased in MI group and Ad group, compared to sham control. In contrast, the expression levels of these proteins were restored in Sema3A group, which may represent the molecular basis of the Sema3A-mediated inhibition of electrical remodeling. In conclusion, Sema3A can ameliorate electrical remodeling at infarct border zones after MI.
梗死周边区的电重构已被证明有助于心肌梗死后（MI）室性心律失常的发生。电重构与 MI 中的交感神经重构具有因果关系。神经导向分子 Sema3A 是交感轴突的有效神经化学抑制剂，已被证明可抑制 MI 后的交感神经重构。在本研究中，我们使用 MI 大鼠模型研究了 Sema3A 治疗是否可以改善梗死周边区的电重构。Wistar 大鼠接受假手术（n = 20）、左冠状动脉结扎（MI 组，n = 30）、MI 对照腺病毒（Ad 组，n = 30）和 Sema3A 腺病毒（Sema3A 组，n = 30）。治疗 8 周后，检查了包括心率变异性（HRV）、单相动作电位时程（MAPD）和有效不应期（ERP）在内的电生理特性，以及左心室梗死边缘与心律失常相关离子通道蛋白（包括 Kv4.2、KChIP2 和 Kir2.1）的表达。这些通道蛋白可能是维持正常心律所必需的。与 Ad 组相比，Sema3A 显著增加了 HRV，缩短了 MAPD 和 ERP（均 P < 0.05）。与 sham 对照组相比，MI 组和 Ad 组的 Kv4.2、KChIP2 和 Kir2.1 蛋白表达水平显著降低。相反，这些蛋白的表达水平在 Sema3A 组得到恢复，这可能代表了 Sema3A 介导的电重构抑制的分子基础。总之，Sema3A 可以改善 MI 后梗死周边区的电重构。
