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
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1.广西中医药大学 第一临床医学院 广西中医药防治医学分子生物重点实验室;2.广西中医药大学第一附属医院 针灸科

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国家中医药管理局高水平重点学科建设项目(zyyzdxk-2023167);国自然科学基金(No.82160934);广西区自然科学基金(No:2022JJA141185),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)。


Experimental study on establishing a circadian rhythm disorder depression rat model under different lighting modes
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1.First Clinical School of Guangxi University of Traditional Chinese Medicine Key Laboratory of Molecular Biology of Traditional Chinese Medicine Prevention and Treatment in Guangxi;2.acupuncture and moxibustion Department of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning

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    摘要:

    【摘要】目的:探究持续光照(constant light, LL)、频繁光周期调整(circadian misalignment,CM)和倒置光周期(inverted photoperiod,IP)三种光照模式建立昼夜节律紊乱抑郁症大鼠模型的效果差异,明确其诱导抑郁样行为及分子改变的异质性。方法:将80只雄性SD大鼠随机分为对照组(circadian alignment,CA,标准LD 12:12光周期)、LL组(24小时持续光照)、CM组(6天循环周期内频繁调整光照)和IP组(完全倒置光周期),干预28天。通过智能笼系统监测运动节律;行为学检测糖水偏好、强迫游泳及旷场实验评估抑郁表型;ELISA检测血浆褪黑素5个时间点昼夜分泌;qPCR分析下丘脑视交叉上核5个时间点生物钟基因(Bmal1、Clock、Per1、Per2)表达;Western Blot检测海马BDNF、IL-6、TNF-α蛋白水平,免疫组化检测海马BDNF平均光密度。结果:与CA组相比,LL组第28天昼夜节律完全消失,昼夜比降至0.76,褪黑素节律性消失(p<0.01),Bmal1和Per1表达持续低平(p<0.01),BDNF降低,IL-6和TNF-α显著升高(p<0.01)。IP组完成12小时相位转移,昼夜节律翻转,抑郁样行为显著增加(p<0.01)。CM组节律紊乱最严重,抑郁样行为最显著,BDNF表达最低,炎症因子水平最高(p<0.01)。结论:三种光照模式均可诱导昼夜节律紊乱抑郁模型,但CM模式通过引发慢性节律失同步(节律破碎、褪黑素衰减及生物钟基因紊乱),导致最严重的抑郁样行为,其机制与BDNF抑制及神经炎症亢进密切相关。维持节律稳定性(如IP组的相位重置)可减轻抑郁损伤,提示避免频繁光照周期变动对预防抑郁症至关重要。

    Abstract:

    Objective: To investigate the differences in the effects of three lighting modes, namely constant light (LL), circular misalignment (CM), and inverted photoperiod (IP), in establishing a rat model of circadian rhythm disorder depression, and to clarify the heterogeneity of depression like behavior and molecular changes induced by LL. Method: 80 male SD rats were randomly divided into a control group (circular alignment, CA, standard LD 12:12 photoperiod), LL group (24-hour continuous photoperiod), CM group (frequent adjustment of photoperiod within a 6-day cycle), and IP group (completely inverted photoperiod), and intervened for 28 days. 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; QPCR 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. Result: 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 hour 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). Conclusion: 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.

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  • 收稿日期:2025-08-08
  • 最后修改日期:2025-12-24
  • 录用日期:2026-01-15
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