Hibberd Timothy J, Ramsay Stewart, Spencer-Merris Phaedra, Dinning Phil G, Zagorodnyuk Vladimir P, Spencer Nick J
College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Adelaide, SA, Australia.
Front Physiol. 2023 Aug 30;14:1239278. doi: 10.3389/fphys.2023.1239278. eCollection 2023.
A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly controlled by the light-entrainable clock located in the suprachiasmatic nucleus of the hypothalamus. Peripheral clocks occur in the gastrointestinal tract, notably the epithelia whose functions include regulation of absorption, permeability, and secretion of hormones; and in the myenteric plexus, which is the intrinsic neural network principally responsible for the coordination of muscular activity in the gut. This review focuses on the physiological circadian variation of major colonic functions and their entraining mechanisms, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. Pathophysiological states such as irritable bowel syndrome and ulcerative colitis and their interactions with circadian rhythmicity are also described. Finally, the classic circadian hormone melatonin is discussed, which is expressed in the gut in greater quantities than the pineal gland, and whose exogenous use has been of therapeutic interest in treating colonic pathophysiological states, including those exacerbated by chronic circadian disruption.
生物钟基因的节律性表达发生在全身多个器官和组织的细胞内,称为“外周生物钟”。外周生物钟会受到多种因素的影响,其中许多因素直接或间接受位于下丘脑视交叉上核的光可调节生物钟控制。外周生物钟存在于胃肠道,尤其是其上皮细胞,其功能包括调节吸收、通透性和激素分泌;还存在于肠肌丛,它是主要负责协调肠道肌肉活动的内在神经网络。本综述重点关注结肠主要功能的生理昼夜变化及其调节机制,包括结肠运动、吸收、激素分泌、通透性和疼痛信号传导。还描述了肠易激综合征和溃疡性结肠炎等病理生理状态及其与昼夜节律的相互作用。最后,讨论了经典的昼夜节律激素褪黑素,其在肠道中的表达量高于松果体,并且其外用在治疗结肠病理生理状态方面具有治疗意义,包括那些因慢性昼夜节律紊乱而加重的状态。