不同光照模式建立昼夜节律紊乱抑郁症大鼠模型的实验研究
Experimental study on establishing a circadian rhythm disorder depression rat model under different lighting modes
摘要
Abstract
Objective To investigate the differences in the effects of three lighting modes,namely constant light(LL),circadian misalignment(CM),and inverted photoperiod(IP),in establishing a rat model of circadian rhythm disorder(CRD)depression,and to clarify the heterogeneity of depression like behavior and molecular changes induced by LL.Methods 72 male SD rats were randomly divided into a control group(circadian alignment,CA,standard LD 12∶12 photoperiod),LL group(24 h continuous photoperiod),CM group(frequent adjustment of photoperiod within a 6 d cycle),and IP group(completely inverted photoperiod),and intervened for 28 d.Monitor movement rhythm through intelligent cage system;behavioral testing of sugar water preference,forced swimming,and open field experiments to evaluate depressive phenotypes;ELISA was used to detect the diurnal secretion of plasma melatonin at 5 time points;qRT-PCR analysis of clock genes(Bmal1,Clock,Per1,Per2)expression in the hypothalamic suprachiasmatic nucleus at five time points;Western Blot was used to detect the protein levels of BDNF,IL-6,and TNF-α in the hippocampus,and immunohistochemistry was used to measure the average optical density of BDNF in the hippocampus.Results Compared with the CA group,the LL group had a complete disappearance of circadian rhythm on the 28th day,with a day night ratio of 0.76,disappearance of melatonin rhythmicity(P＜0.01),sustained low expression of Bmal1 and Per1(P＜0.01),decreased BDNF,and significantly increased IL-6 and TNF-α(P＜0.01).The IP group completed a 12 h phase shift,with a circadian rhythm reversal and a significant increase in depressive like behavior(P＜0.01).The CM group had the most severe rhythm disorder,the most significant depressive like behavior,the lowest BDNF expression,and the highest levels of inflammatory factors(P＜0.01).Conclusions All three lighting modes can induce a circadian rhythm disorder depression model,but the CM mode leads to the most severe depression like behavior by inducing chronic rhythm asynchrony(rhythm disruption,melatonin attenuation,and circadian clock gene disorder),which is closely related to BDNF inhibition and neuroinflammation hyperactivity.Maintaining rhythm stability(such as phase resetting in the IP group)can alleviate depression damage,indicating that avoiding frequent light cycle changes is crucial for preventing depression.关键词
不同光照模式/昼夜节律紊乱/抑郁症/模型研究Key words
different lighting modes/disruption of circadian rhythm/depression/model study分类
生物科学引用本文复制引用
蔡慧倩,粟胜勇,林丽霞,王甜,郑广玫,李欣,陈广辉,凌春燕..不同光照模式建立昼夜节律紊乱抑郁症大鼠模型的实验研究[J].中国实验动物学报,2026,34(2):185-194,10.基金项目
国家中医药管理局中医康复中心建设单位项目(国中医药医政函[2023]255号),第七批广西临床医学研究中心"广西中医康复临床医学研究中心"建设项目(桂科发[2025]293号),广西中医药大学第一附属医院院级科研项目(2021QN014),广西中医药大学校级课题(2022QN015).Funded by National Administration of Traditional Chinese Medicine Traditional Chinese Medicine Rehabilitation Center Development Unit Project(Medical Administration Letter of National Administration of Traditional Chinese Medicine[2023]No.255),the Seventh Batch of Guangxi Clinical Medical Research Centers-"Guangxi Clinical Medical Research Center for Traditional Chinese Medicine Rehabilitation",Construction Project(Guangxi Science and Technology Development[2025]No.293),College Level Research Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine(2021QN014),Campus Level Project of Guangxi University of Chinese Medicine(2022QN015). （国中医药医政函[2023]255号）
