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Ghrelin:术后胃轻瘫发病机制和治疗的新见解。

Ghrelin: new insight to mechanisms and treatment of postoperative gastric ileus.

机构信息

CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.

出版信息

Curr Pharm Des. 2011;17(16):1587-93. doi: 10.2174/138161211796196990.

Abstract

Postoperative gastric ileus develops after abdominal surgery and if prolonged leads to longer hospitalization times. Besides discomfort for the patient such as abdominal bloating and pain, this condition is associated with a great increase in healthcare costs. In order to develop new and effective treatment strategies to alleviate the ileus, a good understanding of the pathophysiogical underlying mechanisms is necessary. Postoperative gastric ileus consists of two phases, a first neural/humoral phase and a second inflammatory phase. The present review will focus on the role of the orexigenic and prokinetic hormone ghrelin in the development of postoperative ileus. Although ghrelin and ghrelin mimetics have been used during the recent years in pre-clinical and a first clinical trial to alleviate symptoms of postoperative ileus, the regulation of this hormone under conditions of abdominal surgery has just recently begun to be explored. Growing evidence indicates that postoperative restoration of ghrelin signaling leads to an orexigenic effect whereas the gastroprokinetic actions seem to require supraphysiological doses. Since the expression of ghrelin-O-acyltransferase (GOAT), the only ghrelin acylating enzyme, is reduced after abdominal surgery, the stimulation of GOAT signaling may also be a new promising approach to restore levels of acyl ghrelin under these conditions and a potential useful addition to ghrelin mimetics.

摘要

术后胃轻瘫发生在腹部手术后,如果持续时间延长,会导致住院时间延长。除了给患者带来不适,如腹胀和疼痛外,这种情况还会导致医疗保健费用大幅增加。为了开发新的、有效的治疗策略来缓解肠梗,有必要对其潜在的病理生理机制有很好的了解。术后胃轻瘫包括两个阶段,第一阶段是神经/体液阶段,第二阶段是炎症阶段。本综述将重点介绍食欲肽和促动力激素胃饥饿素在术后肠梗阻发展中的作用。尽管近年来在临床前和首次临床试验中使用了胃饥饿素和胃饥饿素类似物来缓解术后肠梗阻的症状,但在腹部手术条件下,这种激素的调节才刚刚开始被探索。越来越多的证据表明,术后恢复胃饥饿素信号会导致食欲增加,而胃动力作用似乎需要超生理剂量。由于胃饥饿素-O-酰基转移酶 (GOAT) 的表达在腹部手术后减少,GOAT 信号的刺激也可能是在这些条件下恢复酰基胃饥饿素水平的一种新的有前途的方法,并且可能是胃饥饿素类似物的有益补充。

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