Department of Cardiology, Nanjing Hospital of Chinese Medicineaffiliated to, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Oncology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Sleep Breath. 2024 May;28(2):823-833. doi: 10.1007/s11325-023-02974-2. Epub 2023 Dec 26.
Circadian disruption has been a common issue due to modern lifestyles. Ventricular remodeling (VR) is a pivotal progressive pathologic change after acute myocardial infarction (AMI) and circadian disruption may have a negative influence on VR according to the latest research. Whether or not Guanxin V (GXV) has a positive effect on VR after AMI with circadian disruption drew our interest.
Rats were randomly divided into a sham group, an AMI group, an AMI with circadian disruption group, and an AMI with circadian disruption treated with the GXV group according to a random number table. RNA sequencing (RNA-Seq) was utilized to confirm the different expressed genes regulated by circadian disruption. Cardiac function, inflammation factors, pathological evaluation, and mitochondrial dynamics after the intervention were conducted to reveal the mechanism by which GXV regulated VR after AMI with circadian disruption.
RNA-Seq demonstrated that NF-κB was up-regulated by circadian disruption in rats with AMI. Functional and pathological evaluation indicated that compared with the AMI group, circadian disruption was associcataed with deteriorated cardiac function, expanded infarcted size, and exacerbated fibrosis and cardiomyocyte apoptosis. Further investigation demonstrated that mitochondrial dynamics imbalance was induced by circadian disruption. GXV intervention reversed the inflammatory status including down-regulation of NF-κB. Reserved cardiac function, limited infarct size, and ameliorated fibrosis and apoptosis were also observed in the GXV treated group. GXV maintained mitochondrial fission/fusion imbalance through suppressed expression of mitochondrial fission-associated proteins.
The study findings suggest that identified mitochondrial dysfunctions may underlie the link between circadian disruption and VR. GXV may exert cardioprotection after AMI with circadian disruption through regulating mitochondrial dynamics.
由于现代生活方式，昼夜节律紊乱已成为一个常见问题。心室重构（VR）是急性心肌梗死（AMI）后的关键进行性病理变化，根据最新研究，昼夜节律紊乱可能对 VR 产生负面影响。昼夜节律紊乱的 AMI 后，冠心 V（GXV）是否对 VR 有积极影响引起了我们的兴趣。
根据随机数字表，将大鼠随机分为假手术组、AMI 组、AMI 昼夜节律紊乱组和 AMI 昼夜节律紊乱加 GXV 组。利用 RNA 测序（RNA-Seq）证实昼夜节律紊乱调节的差异表达基因。干预后进行心脏功能、炎症因子、病理评价和线粒体动力学检测，揭示 GXV 调节 AMI 昼夜节律紊乱后 VR 的机制。
RNA-Seq 表明 NF-κB 在 AMI 大鼠昼夜节律紊乱中上调。功能和病理评价表明，与 AMI 组相比，昼夜节律紊乱与心脏功能恶化、梗死面积扩大、纤维化和心肌细胞凋亡加重相关。进一步研究表明，昼夜节律紊乱导致线粒体动力学失衡。GXV 干预通过下调 NF-κB 逆转了炎症状态。在 GXV 治疗组中还观察到保留的心脏功能、限制的梗死面积以及改善的纤维化和凋亡。GXV 通过抑制线粒体分裂相关蛋白的表达维持线粒体分裂/融合失衡。
研究结果表明，确定的线粒体功能障碍可能是昼夜节律紊乱与 VR 之间的联系基础。GXV 可能通过调节线粒体动力学对 AMI 昼夜节律紊乱后发挥心脏保护作用。
