Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.

IF 6.1 2区 生物学 Q1 CELL BIOLOGY
Jingyi Zhang, Xu Zhao, Jing Tang, Ce Liu, Yining Zhang, Cheng Cai, Qingfeng Du
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Abstract

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.

睡眠限制通过线粒体损伤导致心肌细胞死亡和纤维化,从而加剧糖尿病小鼠的心脏功能障碍。
糖尿病心肌病(DCM)是糖尿病的一种心血管并发症,预后不良,是糖尿病患者死亡的主要原因。睡眠不足不仅被认为是 2 型糖尿病发病的重要危险因素,而且还与心血管疾病发病率和死亡率的增加有关。睡眠限制(SR)在 DCM 中的潜在作用和机制尚不清楚。研究以 KK/Upj-Ay T2 DM 小鼠模型为研究对象,利用小动物超声成像系统检测心脏功能;利用免疫病理染色明确心脏组织结构病理改变;利用 TUNEL 染色、qPCR、透射电子显微镜(TEM)和 ELISA 试剂盒检测细胞凋亡、氧化应激、炎症和线粒体损伤及相关分子改变。SR导致DM KK小鼠死亡率明显升高,心脏肥大、坏死、糖原沉积和纤维化进一步恶化。SR 通过 Bax/Bcl2 通路增加了 KK 小鼠心肌细胞的死亡。此外,SR 不仅加剧了炎症反应,还通过 PRDM16-PGC-1α 通路加剧了线粒体损伤并促进了 KK 小鼠的氧化应激。总之,SR 通过炎症、氧化应激和细胞凋亡加剧了 DM KK 小鼠的结构改变和功能障碍,增加了死亡风险。临床医生和糖尿病患者应注意睡眠习惯,避免因睡眠习惯不良而加速DCM向心力衰竭的转变并诱发死亡。
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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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