昼夜节律光/暗周期逆转会加剧小鼠慢性肾脏病的进展。

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-05-27 DOI:10.1111/jpi.12964
Jiayang Zhang, Lejia Qiu, Zhaiyi Liu, Jiaxin Liu, Bo Yu, Chengcheng Liu, Baoyin Ren, Jiaqi Zhang, Shuyao Li, Youfei Guan, Feng Zheng, Guangrui Yang, Lihong Chen
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引用次数: 0

摘要

昼夜节律紊乱,如轮班工作、时差,已逐渐成为一个全球性的健康问题,并与各种代谢紊乱密切相关。昼夜节律紊乱对慢性肾脏病(CKD)肾损伤的影响和机制仍未得到充分了解。在这里,我们评估了环境光干扰对慢性肾脏病小鼠慢性肾损伤进展的影响。通过使用两种异常光照模型来诱导昼夜节律紊乱,我们发现每周光/暗周期逆转(LDDL)诱导的昼夜节律紊乱会显著加重5/6肾切除术和单侧输尿管梗阻(UUO)小鼠的肾功能障碍、加速肾损伤并促进肾纤维化。从机理上讲,RNA-seq分析表明,LDDL调节的CKD肾脏存在明显的免疫和代谢紊乱。LDDL挑战CKD小鼠肾脏组织中ATP含量减少,ROS产生增加。非靶向代谢组学显示,受 LDDL 影响的肾脏中脂类物质明显增多。值得注意的是,我们发现 NAD+ 通路中的重要中间体 β-NMN 的水平尤其降低。此外,我们还证明,服用β-NMN和褪黑激素可显著缓解与光干扰相关的肾功能障碍。总之,环境昼夜节律紊乱可能会通过促进炎症反应和扰乱代谢平衡而加剧慢性肾损伤。β-NMN和褪黑激素治疗可能是预防和治疗与光干扰相关的慢性肾脏病的有效方法。
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Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice

Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA-seq analysis revealed significant immune and metabolic disorder in the LDDL-conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL-challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of β-NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both β-NMN and melatonin administration could significantly rescue the light-disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. β-NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light-disruption associated CKD.

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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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