Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Peptides. 2011 Nov;32(11):2357-61. doi: 10.1016/j.peptides.2011.10.004. Epub 2011 Oct 8.
Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on ventricular remodeling. In this study, we investigated whether ghrelin could decrease vulnerability to ventricular arrhythmias in rats with myocardial infarction and the possible mechanism. Twenty-four hours after ligation of the anterior descending artery, adult male Sprague-Dawley rats were randomized to ghrelin (100 μg/kg) and saline (control group) for 4 weeks. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Myocardial endothelin-1 (ET-1) levels were significantly elevated in saline-treated rats at the border zone compared with sham-operated rats. Myocardial connexin43 (Cx43) expression at the border zone was significantly decreased in saline-treated infarcted rats compared with sham-operated rats. Ghrelin significantly decreased the inducibility of ventricular tachyarrhythmias compared with control group. Arrhythmias sores during programmed stimulation in saline-treated rats were significantly higher than scores in those treated with ghrelin. The electrophysiological improvement of fatal ventricular tachyarrhythmias was accompanied with increased immunofluorescence-stained Cx43, myocardial Cx43 protein and mRNA levels in ghrelin treated rats. We also shown that ghrelin significantly decreased tissue ET-1 levels at the infarcted border zone. Thus, ghrelin showed the protective effect on ventricular arrhythmias after myocardial infarction. Although the precise mechanism by which ghrelin modulates the dephosphorylation of Cx43 remains unknown, it is most likely that the ghrelin increased expression of Cx43 through the inhibition of ET-1.
胃饥饿素是一种新型生长激素释放肽，已被证明对心室重构有有益作用。在本研究中，我们研究了胃饥饿素是否可以降低心肌梗死大鼠对室性心律失常的易感性及其可能的机制。在结扎前降支后 24 小时，雄性成年 Sprague-Dawley 大鼠被随机分为胃饥饿素（100μg/kg）和盐水（对照组）组，治疗 4 周。假手术组只进行开胸和心包切开，但不结扎前降支。与假手术组相比，盐水治疗组大鼠梗塞边缘区心肌内皮素-1（ET-1）水平显著升高。盐水治疗组梗塞大鼠梗塞边缘区心肌连接蛋白 43（Cx43）表达明显低于假手术组。与对照组相比，胃饥饿素明显降低了室性心动过速的易感性。盐水治疗组的心律失常评分明显高于胃饥饿素治疗组。在盐水治疗组大鼠的程控刺激中，心律失常评分明显高于胃饥饿素治疗组。在致命性室性心律失常的电生理改善伴随着免疫荧光染色的 Cx43、心肌 Cx43 蛋白和 mRNA 水平增加。我们还发现，胃饥饿素可显著降低梗塞边缘区的组织 ET-1 水平。因此，胃饥饿素对心肌梗死后室性心律失常有保护作用。尽管胃饥饿素调节 Cx43 去磷酸化的确切机制尚不清楚，但胃饥饿素很可能通过抑制 ET-1 增加 Cx43 的表达。
