过刊浏览

大鼠延髓背侧迷走复合体注射ghrelin 激活弓状核神经肽Y/ 刺鼠色蛋白相关蛋白神经元而诱发多食

管洪在, 李清春, 蒋正尧

青岛大学医学院生理学教研室，青岛 266071； 滨州医学院附属医院生殖医学科，滨州 256603

摘要

Ghrelin 是生长素促分泌受体的内源性配体，刺激摄食并增加体重。已有研究证实ghrelin 刺激摄食的作用靶点主要是下丘脑弓状核(hypothalamic arcuate nucleus, ARC)内的神经肽Y (neuropeptide Y, NPY)/ 刺鼠色蛋白相关蛋白(agouti-related peptide,AgRP)神经元。除下丘脑外，脑干尾部迷走复合体具有ghrelin 受体，是ghrelin 调控摄食活动的另一靶点。本实验旨在验证ghrelin 作用于脑干尾部所诱发的摄食增加是否需要下丘脑NPY/AgRP 神经元参与。在大鼠延髓背侧迷走复合体(dorsal vagalcomplex, DVC )微量注射20 pmol 的ghrelin，用摄食自动分析仪测量大鼠的摄食反应，用荧光定量PCR 技术测定ARC 的NPY/AgRP mRNA 的表达水平，同时利用免疫组化技术测定ARC 的NPY 阳性神经元数量及光密度。结果显示，与对照组(DVC微量注射生理盐水)相比，ghrelin 微注射组大鼠摄食量增加，其累积摄食量在注射后2 h 达最高峰；ARC 处NPY/AgRP mRNA的表达水平、NPY 免疫阳性神经元的数量及光密度也明显增加，且均在ghrelin 注射后2 h 增高达到高峰。以上结果提示，大鼠DVC 注射 ghrelin 可能通过上行纤维激活弓状核NPY/AgRP 神经元，介导大鼠的多食反应。

关键词： ghrelin ; 摄食; 背侧迷走复合体; 弓状核; 神经肽Y/ 刺鼠色蛋白相关蛋白; 大鼠

分类号：R335

Ghrelin acts on rat dorsal vagal complex to stimulate feeding via arcuate neuropeptide Y/agouti-related peptide neurons activation

GUAN Hong-Zai, LI Qing-Chun, JIANG Zheng-Yao

Department of Physiology, Qingdao University School of Medicine, Qingdao 266071, China； Department of Reproductive Medicine, the Affiliated Hospital of Binzhou Medical College, Binzhou 256603, China

Abstract

Ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor, stimulates feeding and increases bodyweight. The primary action site of ghrelin has been reported to be the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons inthe hypothalamic arcuate nucleus (ARC). In addition to the hypothalamus, the caudal brainstem also appears to be an importantmediator for the orexigenic activity of ghrelin. However, it is not clear whether ghrelin applied directly to the caudal brainstem activatesforebrain structures. The aim of this study was to determine whether recruitment of forebrain structures was required for hyperphagicresponses stimulated by ghrelin delivery within the caudal brainstem. In our experiment, all rats were surgically implanted withindwelling cannulas in the dorsal vagal complex (DVC), and ghrelin (20 pmol in 0.5 μL) was delivered to the DVC. After the injection,the orexigenic response to ghrelin was recorded by Feeding and Activity Analyser, and NPY/AgRP mRNA expressions in rat hypothalamuswere detected by real-time PCR. In addition, the NPY immunoreactive neurons in the ARC were assayed by immunohistochemistry.The results showed that ghrelin significantly increased cumulative food intake at 1, 2 and 3 h after ghrelin injection, maximal responseoccurring at 2 h after injection. NPY/AgRP mRNA levels in ARC treated with ghrelin increased significantly compared with those incontrol group (injected with saline). The highest levels of NPY and AgRP mRNA were detected at 2 h after injection. The total numberand mean optical density of NPY-positive neurons increased in ghrelin treated rats compared with those in control group. Consistently,ghrelin’s effect was most pronounced at 2 h after injection. Taken together, we conclude that the activation of NPY/AgRP neurons inthe ARC is involved in the mediation of the hyperphagic response to brainstem ghrelin administration in neurologically intact rats.

Key words: ghrelin; food intake; dorsal vagal complex; arcuate nucleus; neuropeptide Y/agouti-related peptide; rat

收稿日期：2010-06-09　　录用日期：2010-07-20

通讯作者：蒋正尧　　E-mail: qd-zyj@163.com

引用本文：

管洪在, 李清春, 蒋正尧. 大鼠延髓背侧迷走复合体注射ghrelin 激活弓状核神经肽Y/ 刺鼠色蛋白相关蛋白神经元而诱发多食[J]. 生理学报 2010; 62 (4): 357-364.

GUAN Hong-Zai, LI Qing-Chun, JIANG Zheng-Yao. Ghrelin acts on rat dorsal vagal complex to stimulate feeding via arcuate neuropeptide Y/agouti-related peptide neurons activation. Acta Physiol Sin 2010; 62 (4): 357-364 (in Chinese with English abstract).