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OA

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.