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胰高血糖素样肽-1受体激动剂抑制大鼠进食效应的比较研究

文松, 阮氏琼娥, 萧文泽, 王朝迅, 龚敏, 金建兰, 周里钢^*

复旦大学附属浦东医院内分泌科，上海 201399

摘要

胰高血糖素样肽-1 (glucagon-like peptide-1, GLP-1)在小肠细胞和脑干神经元中都有表达，起着抑制进食的作用。然而，目前对生理状态下影响进食的GLP-1的来源或是GLP-1受体激动剂(GLP-1 receptor agonists, GLP-1RA)的相关作用机制尚不明确。本研究选择即刻早期基因产物c-Fos作为特异抗原进行免疫组化染色以显示被GLP-1RA激活的中枢神经系统特定区域。将30只正常SD大鼠随机分为3组，分别一次性腹腔注射利拉鲁肽(200 μg/kg)、艾塞那肽(10 μg/kg)和生理盐水，检测给药后早期大鼠的摄食总量和血糖。结果显示，急性腹腔注射药理浓度的GLP-1RA能显著地影响摄食。然而，血糖的比较研究显示，在正常大鼠，GLP-1RA抑制进食的作用可能与血糖的变化相分离。与对照组相比，GLP-1RA组c-Fos表达主要在与摄食相关的核团中显著升高，并且在脊髓中发现了c-Fos的表达。以上结果果提示，急性注射药理浓度的GLP-1可以通过循环和迷走神经的途径影响中枢神经系统，尤其是作用于弓状核(arcuate nucleus, ARC)和孤束核(nucleus of solitary tract, NTS)，GLP-1能同时调节自主神经的活动。

关键词： 胰高血糖素样肽-1; c-Fos; 摄食; 脑核团; 脊髓

分类号：Q954.62

Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats

WEN Song, Thiquynhnga NGUYEN, XIAO Wen-Ze, WANG Chao-Xun, GONG Min, JIN Jian-Lan, ZHOU Li-Gang^*

Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, China

Abstract

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated.  In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 μg/kg), Exenatide (10 μg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities. 

Key words: glucagon-like peptide-1; c-Fos; food intake; brain nuclei; spinal cord

收稿日期：2019-01-14　　录用日期：2019-03-12

通讯作者：周里钢　　E-mail: zhouligang@yahoo.com

DOI: 10.13294/j.aps.2019.0043

引用本文：

文松, 阮氏琼娥, 萧文泽, 王朝迅, 龚敏, 金建兰, 周里钢. 胰高血糖素样肽-1受体激动剂抑制大鼠进食效应的比较研究[J]. 生理学报 2019; 71 (4): 514-526.

WEN Song, Thiquynhnga NGUYEN, XIAO Wen-Ze, WANG Chao-Xun, GONG Min, JIN Jian-Lan, ZHOU Li-Gang. Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats. Acta Physiol Sin 2019; 71 (4): 514-526