Semaphorin 3A attenuates electrical remodeling at infarct border zones in rats after myocardial infarction.
Semaphorin 3A attenuates electrical remodeling at infarct border zones in rats after myocardial infarction.
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DOI：
10.1620/tjem.225.51
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Hua-zhi Wen;Hong Jiang;Li Li-Li;P. Xie;Jin-yao Li;Zhibing Lu;B. He
中科院分区：
文献类型：
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作者：
Hua-zhi Wen;Hong Jiang;Li Li-Li;P. Xie;Jin-yao Li;Zhibing Lu;B. He
心肌梗死边缘区的电重构是心肌梗死后室性心律失常发生的重要原因。心肌梗死时电重构与交感神经重构存在因果关系。脑信号蛋白3A（Semaphorin 3A，Sema3A）是一种有效的交感神经轴突化学排斥剂，已被证实能抑制心肌梗死后交感神经的重塑。在本研究中，我们研究了Sema3A治疗是否可以改善梗死边缘区的电重构使用大鼠模型MI。Wistar大鼠分为假手术组（n = 20）、左冠状动脉结扎组（MI组，n = 30）、腺病毒对照组（Ad组，n = 30）和Sema3A腺病毒组（Sema3A组，n = 30）。治疗8周后，检测心肌梗死边缘区心肌电生理参数（心率变异性（HRV）、单相动作电位时程（MAPD）、有效不应期（ERP））及心肌梗死相关离子通道蛋白Kv4.2、KChIP 2、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组HRV显著增加，MAPD和ERP显著缩短（均P < 0.05）。MI组和Ad组Kv4.2、KChIP2和Kir2.1蛋白表达水平较假手术组明显降低。而Sema3A组这些蛋白的表达水平恢复正常，这可能是Sema3A抑制电重构的分子基础。总之，Sema3A可以改善MI后梗死边缘区的电重构。
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.