Ghrelin Prevents Incidence of Malignant Arrhythmia after Acute Myocardial Infarction through Vagal Afferent Nerves
Ghrelin Prevents Incidence of Malignant Arrhythmia after Acute Myocardial Infarction through Vagal Afferent Nerves
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DOI：
10.1210/en.2012-1065
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发表时间：
2012-07-01
期刊：
影响因子：
4.8
通讯作者：
Kangawa, Kenji
中科院分区：
文献类型：
--
作者：
Mao, Yuanjie;Tokudome, Takeshi;Kangawa, Kenji
Ghrelin 是一种主要从胃分泌的 GH 释放肽。 Ghrelin 给药已被证明可以抑制心脏交感神经活动 (CSNA)，减少恶性心律失常，并改善急性心肌梗死 (MI) 后的预后。因此，我们通过使用 ghrelin 敲除 (KO) 小鼠研究了内源性 ghrelin 的作用对 MI 后存活率和 CSNA 的影响和潜在机制。通过结扎 46 只 KO 小鼠和 41 只野生型小鼠的左冠状动脉诱导 MI。第一天，结扎后30分钟内观察到恶性心律失常引起的死亡，野生型小鼠的发生率为2.4%，KO小鼠的发生率为17.4%（P < 0.05）。接下来我们通过心率变异性频谱分析来评估 CSNA。以低频/高频比为代表的 CSNA 在基线时 KO 小鼠中较高（2.18 +/- 0.43 对比 0.98 +/- 0.09；P < 0.05），尤其是 MI 后（25.5 +/- 11.8 对比 1.4 +/- 0.3；P < 0.05），高于野生型小鼠。连接前15分钟的Ghrelin（150μg/kg，皮下）抑制CSNA的激活并降低KO小鼠的死亡率。此外，生长素释放肽的这种作用可以被溴化甲基阿托品（1 mg/kg，腹腔注射）或用辣椒素（一种特定的传入神经毒素）对两个颈迷走神经干进行神经周围治疗来抑制。我们的数据表明，外源性和内源性生长素释放肽均可抑制CSNA，预防恶性心律失常的发生，并改善急性心肌梗死后的预后。这些影响可能是通过迷走传入神经产生的。 （内分泌学153：3426-3434，2012）
Ghrelin is a GH-releasing peptide mainly excreted from the stomach. Ghrelin administration has been shown to inhibit cardiac sympathetic nerve activity (CSNA), reduce malignant arrhythmia, and improve prognosis after acute myocardial infarction (MI). We therefore investigated the effects and potential mechanisms of the action of endogenous ghrelin on survival rate and CSNA after MI by using ghrelin-knockout (KO) mice. MI was induced by left coronary artery ligation in 46 KO mice and 41 wild-type mice. On the first day, malignant arrhythmia-induced mortality was observed within 30 min of the ligation and had an incidence of 2.4% in wild-type and 17.4% in KO mice (P < 0.05). We next evaluated CSNA by spectral analysis of heart rate variability. CSNA, represented by the low frequency/high frequency ratio, was higher in KO mice at baseline (2.18 +/- 0.43 vs. 0.98 +/- 0.09; P < 0.05), and especially after MI (25.5 +/- 11.8 vs. 1.4 +/- 0.3; P < 0.05), than in wild-type mice. Ghrelin (150 mu g/kg, sc) 15 min before ligation suppressed the activation of CSNA and reduced mortality in KO mice. Further, this effect of ghrelin was inhibited by methylatropine bromide (1 mg/kg, ip) or by perineural treatment of both cervical vagal trunks with capsaicin (a specific afferent neurotoxin). Our data demonstrated that both exogenous and endogenous ghrelin suppressed CSNA, prevented the incidence of malignant arrhythmia, and improved the prognosis after acute MI. These effects are likely to be via the vagal afferent nerves. (Endocrinology 153: 3426-3434, 2012)