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Ghrelin 受体在小肠中的下调会延迟迷走神经切断大鼠的小肠转运。

Down-regulation of ghrelin receptors in the small intestine delays small intestinal transit in vagotomized rats.

机构信息

Department of General Surgery, The Sixth Hospital Affiliated with Shanghai Jiao Tong University, Shanghai 200233, PR China.

出版信息

Mol Med Rep. 2011 Nov-Dec;4(6):1061-5. doi: 10.3892/mmr.2011.571. Epub 2011 Aug 24.

DOI:10.3892/mmr.2011.571
PMID:21874246
Abstract

Vagal nerve injury may occur in esophageal and gastric surgeries. The aim of this study was to observe the effects of ghrelin on small intestinal motility upon vagal nerve injury and the possible co-relationship between changes in ghrelin receptor expression in the small intestine and delayed small intestinal transit after vagotomy. The effects of intraperitoneal administration of ghrelin (20, 40 and 80 µg/kg) and the ghrelin receptor antagonist [D-Lys3]-GHRP-6 (1.5 µmol/kg) on small intestinal transit were studied in control and vagotomized rats in vivo. The effects of ghrelin (0.01, 0.1, 0.5, 1.0 and 2.0 µmol/l) on the contraction force of smooth muscle strips from the jejunum were studied in the presence or absence of carbachol (50 nmol/l) and [D-Lys3]-GHRP-6 (10 µmol/l) in vitro. Ghrelin receptor expression was assessed in intestinal muscle layers by means of Western blotting. The results indicated that ghrelin dose-dependently increased small intestinal transit in the control and model rats. In addition, ghrelin enhanced smooth muscle strip contraction induced by carbachol. Ghrelin receptor antagonist [D-Lys3]-GHRP-6 blocked the effect of ghrelin. Ghrelin receptor expression in the small intestinal muscle layers was down-regulated in the vagotomized rats. Down-regulation of growth hormone secretagogue receptor 1a in small intestinal muscle layers, which affected the function of ghrelin, may be one of the mechanisms behind delayed small intestinal transit after vagotomy.

摘要

迷走神经损伤可能发生在食管和胃手术中。本研究旨在观察胃饥饿素对迷走神经损伤后小肠运动的影响,以及迷走神经切断后小肠通过时间延迟与小肠内胃饥饿素受体表达变化之间的可能相关性。体内研究观察了腹腔内给予胃饥饿素(20、40 和 80µg/kg)和胃饥饿素受体拮抗剂[D-Lys3]-GHRP-6(1.5µmol/kg)对正常和迷走神经切断大鼠小肠通过的影响。在存在或不存在卡巴胆碱(50nmol/l)和[D-Lys3]-GHRP-6(10µmol/l)的情况下,体外研究了胃饥饿素(0.01、0.1、0.5、1.0 和 2.0µmol/l)对空肠平滑肌条收缩力的影响。通过 Western 印迹法评估了肠道肌肉层中的胃饥饿素受体表达。结果表明,胃饥饿素在正常和模型大鼠中均呈剂量依赖性地增加小肠通过。此外,胃饥饿素增强了卡巴胆碱诱导的平滑肌条收缩。胃饥饿素受体拮抗剂[D-Lys3]-GHRP-6 阻断了胃饥饿素的作用。迷走神经切断大鼠小肠肌肉层中的生长激素促分泌素受体 1a 表达下调。生长激素促分泌素受体 1a 在小肠肌肉层中的下调,影响了胃饥饿素的功能,可能是迷走神经切断后小肠通过时间延迟的机制之一。

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Mol Med Rep. 2011 Nov-Dec;4(6):1061-5. doi: 10.3892/mmr.2011.571. Epub 2011 Aug 24.
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PLoS One. 2012;7(4):e35265. doi: 10.1371/journal.pone.0035265. Epub 2012 Apr 6.