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20pmol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2h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2h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。
Ghrelin,an endogenous ligand for the growth hormone secretagogue（GHS） receptor,stimulates feeding and increases body weight.The primary action site of ghrelin has been reported to be the neuropeptide Y（NPY）/agouti-related peptide（AgRP） neurons in the hypothalamic arcuate nucleus（ARC）.In addition to the hypothalamus,the caudal brainstem also appears to be an important mediator for the orexigenic activity of ghrelin.However,it is not clear whether ghrelin applied directly to the caudal brainstem activates forebrain structures.The aim of this study was to determine whether recruitment of forebrain structures was required for hyperphagic responses stimulated by ghrelin delivery within the caudal brainstem.In our experiment,all rats were surgically implanted with indwelling 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 hypothalamus were 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 response occurring at 2 h after injection.NPY/AgRP mRNA levels in ARC treated with ghrelin increased significantly compared with those in control group（injected with saline）.The highest levels of NPY and AgRP mRNA were detected at 2 h after injection.The total number and 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 in the ARC is involved in the mediation of the hyperphagic response to brainstem ghrelin administration in neurologically intact rats.
出处
《生理学报》
CAS
CSCD
北大核心
2010年第4期357-364,共8页
Acta Physiologica Sinica
基金
supported by the National Natural Science Foundation of China(No.30670679,30870816)
