Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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冠心V通过调节线粒体动力学减轻昼夜节律紊乱的急性心肌梗死后心室重塑

目的

由于现代生活方式，昼夜节律紊乱已成为一个常见问题。最新研究表明，心室重塑（VR）是急性心肌梗死（AMI）后关键的进行性病理改变，昼夜节律紊乱可能对VR产生负面影响。冠心 V (GXV) 是否对 AMI 后昼夜节律紊乱的 VR 产生积极影响引起了我们的兴趣。

方法

按随机数字表法将大鼠随机分为假手术组、AMI组、AMI伴昼夜节律紊乱组、AMI伴昼夜节律紊乱组GXV组。RNA测序（RNA-Seq）用于确认受昼夜节律破坏调节的不同表达基因。对干预后的心脏功能、炎症因子、病理学评估和线粒体动力学进行评估，以揭示 GXV 在昼夜节律紊乱的 AMI 后调节 VR 的机制。

结果

RNA-Seq 证明 AMI 大鼠的昼夜节律紊乱导致 NF-κB 上调。功能和病理评估表明，与AMI组相比，昼夜节律紊乱与心功能恶化、梗塞面积扩大、纤维化和心肌细胞凋亡加剧有关。进一步的研究表明，线粒体动力学失衡是由昼夜节律紊乱引起的。GXV 干预逆转了炎症状态，包括下调 NF-κB。GXV 治疗组还观察到保留的心脏功能、有限的梗塞面积以及纤维化和细胞凋亡的改善。GXV 通过抑制线粒体裂变相关蛋白的表达来维持线粒体裂变/融合失衡。

结论

研究结果表明，已发现的线粒体功能障碍可能是昼夜节律紊乱与 VR 之间联系的基础。GXV 可能通过调节线粒体动力学在昼夜节律紊乱的 AMI 后发挥心脏保护作用。