Digestive System & Nutrition Laboratory (ADEN EA4311), Institute of Medical Research and Innovation, Rouen University & Hospital, IFR23, Rouen 76183, France.
Eur J Neurosci. 2011 Jan;33(2):276-84. doi: 10.1111/j.1460-9568.2010.07474.x. Epub 2010 Nov 9.
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.
胃电刺激（GES）是治疗功能性消化不良和胃轻瘫的新方法。除了改善恶心和呕吐外，GES 还可改善食欲，而这种改善并不总是与加速胃排空有关。为了探讨 GES 改善食欲的中枢和外周因素，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 1 小时 GES 的作用与假刺激进行了比较。GES 后，刺激区域的黏膜和黏膜下层的 c-Fos 表达增加了 174%。在胃中，GES 增加了 ghrelin mRNA（178%）并使 ghrelin 阳性细胞数量增加一倍，导致血浆 ghrelin 水平升高（2.3 ± 0.2 对 1.6 ± 0.2 ng/mL）。在下丘脑弓状核中，GES 增加了 c-Fos（277%）和 agouti 相关蛋白（AgRP）mRNA 表达（135%）。GES 减少了孤束核中 c-Fos 阳性细胞的数量（从吻侧向尾侧水平减少 93%至 75%），包括儿茶酚胺能神经元（尾侧水平减少 81%）。GES 对胃排空、血浆葡萄糖和心率变异性没有影响。这项研究表明，GES 可能通过刺激主要的食欲途径来改善食欲，包括胃中 ghrelin 的产生和下丘脑的 AgRP，以及通过减少脑干儿茶酚胺能神经元的活性。
