摘要
疲劳是指开展或维持随意活动过程中出现障碍的表现,既可作为独立的疾病,又可作为多种疾病中出现的症状。疲劳发生率高,严重影响人们的身心健康,防治疲劳成为亟待解决的重要问题。疲劳的发病机制主要包括能量损耗、代谢产物堆积、递质分泌失常、线粒体功能下降、下丘脑-垂体-肾上腺轴功能失调等,目前国内外还没有形成统一的认识。疲劳的基因学研究是目前的研究前沿,基因表达谱研究为疲劳的机制研究提供了新的方法,基因芯片技术与中医学理论相结合,有望给疲劳的发病机制研究带来突破性进展。在疲劳的基因芯片研究中,信使RNA(mRNA)和微小RNA(miRNA)是常见的研究对象,而围绕某一具体信号通路对疲劳的基因表达规律及中医药治疗疲劳有效调控靶点的探索较少。近年来,中枢神经系统奖励和抑制作用的功能失调成为研究热点,尤其是γ氨基丁酸(GABA)和多巴胺(DA)分别作为抑制作用和奖励机制的主导物质备受关注。GABA和DA主导的抑制作用和奖励机制维持平衡则机体无疲劳感,而平衡一旦被打破,则疲劳感形成。同时,DA和GABA受体还可通过调控环磷酸腺苷(cAMP)信号通路来影响机体的疲劳感。运用基因芯片技术对GABA/DA平衡机制及相关cAMP信号通路中的关键基因进行研究有望深入揭示疲劳的发病机制。采用基因芯片的方法,检测疲劳人群和正常人群中GABA/DA信号通路及相关cAMP信号通路中关键基因表达的变化,可以深入探讨疲劳的发病机制。基于此,该文对和疲劳相关的GABA/DA平衡机制及相关cAMP信号通路中的关键基因进行总结归纳,为从基因学研究角度有针对性地深入探讨疲劳的发病机制并进行有效防治提供依据。
Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities,which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people’s physical and mental health,and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation, accumulation of metabolites, abnormal secretion of neurotransmitters,decline of mitochondrial function,dysfunction of hypothalamus pituitary adrenal axis,etc. At present,there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine(TCM)theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip, messenger RNA(mRNA) and microRNA(miRNA) are the common research objects, but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years, the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular,gamma amino butyric acid(GABA)and dopamine(DA)have attracted much attention as the main substances of inhibition and reward mechanism,respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance,and the body will not feel fatigue. Once the balance is broken,the fatigue will be formed. At the same time,DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway(cAMP)to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population,so as to further explore the pathogenesis of fatigue. In this paper,the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method,so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.
作者
杨星哲
李峰
吴凤芝
李杰
徐一菲
王雪娇
王若冲
何青鋆
谭丽博
YANG Xing-zhe;LI Feng;WU Feng-zhi;LI Jie;XU Yi-fei;WANG Xue-jiao;WANG Ruo-chong;HE Qing-yun;TAN Li-bo(Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第8期209-217,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81874428)
中国博士后科学基金面上项目(2019M660570)。
