胰高血糖素样肽介导运动抗抑郁作用潜在机制.docVIP

胰高血糖素样肽介导运动抗抑郁作用潜在机制 　　摘 要：胰高血糖素样肽-1（GLP-1）是机体在响应营养摄入时而释放的一类肠促胰岛素，主要由肠道末端L细胞分泌，是目前治疗糖尿病的重要靶点。近年来，研究发现：GLP-1受体不仅在肠、胰腺等外周组织中表达，而且在海马、下丘脑等脑组织中也大量表达，这暗示其可能在糖尿病的并发疾病――抑郁症中发挥作用；但GLP-1易被二肽基肽酶Ⅳ降解失活，难以发挥作用，而长期运动可增加GLP-1的表达和分泌。基于此，旨在探究运动介导GLP-1调控抑郁行为的可能机制，进而为运动的抗抑郁机制研究提供新的视角。通过对相关领域文献资料的梳理分析发现，GLP-1介导运动的抗抑郁作用涉及HPA轴激活、中枢单胺类神经递质、中枢营养因子及中枢炎症因子的水平4个维度。由此推论，GLP-1可能是运动发挥抗抑郁作用的重要介质，从而为抑郁症的能量代谢机制和治疗策略提供了新的靶点和阐释路径。 　　关键词：抑郁症；胰高血糖素样肽；运动；HPA轴；单胺类神经递质；神经营养因子；炎症 　　中图分类号：G 804.2 文章编号：1009-783X（2017）05-0474-07 文献标识码：A 　　Abstract： Glucagon-like peptide -1 （GLP-1）， mainly secreted by L cells， is a kind of incretin hormone released by the body in response to nutritional intake and an important target for the treatment of diabetes. Recent studies have found that GLP-1 receptor is not only expressed in intestinal and pancreatic， but also in the hippocampus and hypothalamus， suggesting its role in depression accompany with diabetes. However， GLP-1 can be degradated by dipeptidyl peptidase Ⅳ， thus being difficult to work， while long term exercise can increase the expression and secretion of GLP-1. Therefore， the current study aimed to explore potential mechanisms of GLP-mediated antidepressant effects of exercise， and to provide a new perspective for exercise effects on depression. The available documents demonstrate that the activation of HPA axis， the expression of central monoamine neurotransmitters， neurotrophic factor and central inflammatory cytokines are involved in the antidepressant effects. To sum up， GLP-1 may be a mediator of exercise effects on depression， which suggests a novel target and pathway of energy metabolism and treatment strategy for depression. 　　Keywords： depression； glucagon-like peptide； exercises； HPA axis； monoamine neurotransmitters； neurotrophic factors； inflammation 　　研究已?充分证实，抑郁症患者存在HPA轴功能失调、单胺类功能异常、脑源性神经营养因子减少及中枢炎症反应增加。临床上，糖尿病患者罹患抑郁症现象正受到越来越多研究者的关注，反之亦然[1]。胰高血糖素样肽（glucagon-like peptide），包括胰高血糖素样肽-1（GLP-1）和2（GLP-2），是目前治疗糖尿病的重要靶点。最新研究表明，GLP-1、GLP-2或其受体激动剂、水解