Gastric electrical stimulation increases ghrelin production and inhibits catecholaminergic brainstem neurons in rats
Gastric electrical stimulation increases ghrelin production and inhibits catecholaminergic brainstem neurons in rats
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DOI：
10.1111/j.1460-9568.2010.07474.x
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发表时间：
2011-01-01
影响因子：
3.4
通讯作者：
Fetissov, Serguei O.
中科院分区：
文献类型：
--
作者：
Gallas, Syrine;Sinno, Maria Hamze;Fetissov, Serguei O.
胃电刺激（GES）是治疗功能性消化不良和胃轻瘫的一种新方法。除了改善恶心和呕吐外，GES还可改善食欲，这并不总是与胃排空加速相关。为了探讨GES相关食欲改善的中枢和外周因素，我们在麻醉的Wistar大鼠中建立了GES模型。在剖腹手术中，将两个电极植入胃中，并施加高频低能量GES（14 Hz，5 mA）。将1h GES的效应与假刺激进行比较。GES后，c-Fos在刺激区粘膜和粘膜下层表达增加（174%）。在胃中，GES增加了ghrelin mRNA（178%），并使ghrelin阳性细胞数量增加了一倍，导致ghrelin血浆水平升高（2.3 +/- 0.2 vs 1.6 +/- 0.2 ng/mL）。在下丘脑弓状核，GES增加c-Fos（277%）和agouti相关蛋白（AgRP）mRNA表达（135%）。GES减少整个孤束核的c-Fos阳性细胞的数量（从吻侧到尾侧水平在93%和75%之间），包括儿茶酚胺能神经元（在尾侧水平为81%）。胃排空、血糖和心率变异性不受GES的影响。这项研究表明，GES可以通过刺激主要的食欲产生途径来改善食欲，包括胃中的ghrelin产生和下丘脑中的AgRP，以及通过降低儿茶酚胺能脑干神经元的活性。
Gastric electrical stimulation (GES) is a new therapeutic option for functional dyspepsia and gastroparesis. In addition to ameliorating nausea and vomiting, GES results in improved appetite which is not always associated with accelerated gastric emptying. To explore the central and peripheral factors underlying GES-associated improvement of appetite we developed a GES model in anaesthetized Wistar rats. During laparotomy, two electrodes were implanted into the stomach and high-frequency low-energy GES (14 Hz, 5 mA) was applied. The effects of 1 h GES were compared with sham stimulation. After GES, c-Fos expression was increased in the mucosal and submucosal layers of the stimulated area (174%). In the stomach, GES increased ghrelin mRNA (178%) and doubled the number of ghrelin-positive cells, resulting in elevated plasma levels of ghrelin (2.3 +/- 0.2 vs. 1.6 +/- 0.2 ng/mL). In the arcuate nucleus of the hypothalamus, GES increased c-Fos (277%) and agouti-related protein (AgRP) mRNA expression (135%). GES reduced the number of c-Fos-positive cells throughout the nucleus of the solitary tract (between 93 and 75% from rostral to caudal levels) including catecholaminergic neurons (81% at caudal level). Gastric emptying, plasma glucose and heart rate variability were not affected by GES. This study shows that GES may improve appetite via stimulation of main orexigenic pathways, including ghrelin production in the stomach and AgRP in the hypothalamus, as well as by reducing the activity of catecholaminergic brainstem neurons.