Excessive Sympathoactivation and Deteriorated Heart Function After Myocardial Infarction in Male Ghrelin Knockout Mice
Excessive Sympathoactivation and Deteriorated Heart Function After Myocardial Infarction in Male Ghrelin Knockout Mice
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DOI：
10.1210/en.2012-2132
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发表时间：
2013-05-01
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
我们以前已经证明了内源性生长激素释放肽对心肌梗死（MI）非常急性期恶性心律失常的保护作用。然而，内源性生长激素释放肽在慢性期的作用是未知的。因此，本研究的目的是关注内源性ghrelin对急性MI后心功能和交感神经激活的影响。在46只ghrelin敲除（KO）和41只野生型（WT）雄性小鼠中，通过左冠状动脉结扎产生MI。2周内心力衰竭病死率WT组为0%，KO组为10.9%（P < 0.05）。在这一时期结束时，KO小鼠的肺重量/胫骨长度、心钠素和脑钠素转录物、收缩末期和舒张末期容积都显著更大，而以射血分数表示的收缩功能（16.4 +/-4.7%vs 25.3 +/- 5.1%）、收缩末期弹性和前负荷可恢复的每搏功显著低于WT小鼠（P < 0.05）。遥测记录和心率变异性分析表明，KO小鼠有更强的交感神经激活后MI比WT小鼠。KO小鼠中的美托洛尔治疗和生长素释放肽治疗防止了过度的交感神经激活，降低了血浆肾上腺素和去甲肾上腺素水平，并改善了MI后的心脏功能和存活率。我们的数据表明，内源性ghrelin在心肌梗死后保护心脏功能和降低死亡率方面起着至关重要的作用，这些作用似乎部分是交感神经抑制的结果。（内分泌学154：1854-1863，2013）
We have previously demonstrated the protective role of endogenous ghrelin against malignant arrhythmias in the very acute phase of myocardial infarction (MI). However, the role of endogenous ghrelin in the chronic phase is unknown. Therefore, the aim of the current study was to focus on the effects of endogenous ghrelin on cardiac function and sympathetic activation after acute MI. In 46 ghrelin-knockout (KO) and 41 wild-type (WT) male mice, MI was produced by left coronary artery ligation. The mortality due to heart failure within 2 weeks was 0% in WT and 10.9% in KO (P < 0.05). At the end of this period, lung weight/tibial length, atrial natriuretic peptide and brain natriuretic peptide transcripts, end-systolic and end-diastolic volumes were all significantly greater in KO mice, whereas systolic function, represented by ejection fraction (16.4 +/- 4.7% vs 25.3 +/- 5.1%), end-systolic elastance, and preload-recruitable stroke work, was significantly inferior to that in WT mice (P < 0.05). Telemetry recording and heart rate variability analysis showed that KO mice had stronger sympathetic activation after MI than did WT mice. Metoprolol treatment and ghrelin treatment in KO mice prevented excessive sympathetic activation, decreased plasma epinephrine and norepinephrine levels, and improved heart function and survival rate after MI. Our data demonstrate that endogenous ghrelin plays a crucial role in protecting heart function and reducing mortality after myocardial infarction, and that these effects seem to be partly the result of sympathetic inhibition. (Endocrinology 154: 1854-1863, 2013)