Guan Hong-Zai, Li Qing-Chun, Jiang Zheng-Yao
Department of Physiology, Qingdao University School of Medicine, Qingdao, China.
Sheng Li Xue Bao. 2010 Aug 25;62(4):357-64.
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.
胃饥饿素是生长激素促分泌素（GHS）受体的内源性配体，可刺激进食并增加体重。据报道，胃饥饿素的主要作用部位是下丘脑弓状核（ARC）中的神经肽Y（NPY）/刺鼠相关肽（AgRP）神经元。除下丘脑外，延髓尾端似乎也是胃饥饿素促食欲活性的重要介导部位。然而，尚不清楚直接作用于延髓尾端的胃饥饿素是否会激活前脑结构。本研究的目的是确定延髓尾端注射胃饥饿素所引发的摄食亢进反应是否需要前脑结构的参与。在我们的实验中，所有大鼠均通过手术在迷走神经背核复合体（DVC）植入留置套管，并将胃饥饿素（20 pmol，溶于0.5 μL）注射到DVC。注射后，通过进食和活动分析仪记录对胃饥饿素的促食欲反应，并通过实时PCR检测大鼠下丘脑NPY/AgRP mRNA的表达。此外，通过免疫组织化学检测ARC中NPY免疫反应性神经元。结果显示，胃饥饿素注射后1、2和3小时，累积食物摄入量显著增加，最大反应出现在注射后2小时。与对照组（注射生理盐水）相比，注射胃饥饿素的ARC中NPY/AgRP mRNA水平显著升高。注射后2小时检测到NPY和AgRP mRNA的最高水平。与对照组相比，胃饥饿素处理组大鼠中NPY阳性神经元的总数和平均光密度增加。一致的是，胃饥饿素的作用在注射后2小时最为明显。综上所述，我们得出结论，ARC中NPY/AgRP神经元的激活参与了对神经功能正常的大鼠脑干注射胃饥饿素后摄食亢进反应的介导。
