Abstract: Background Sleep fragmentation（SF） is one of the hallmarks of sleep disorders，and the mechanism of its role in cardiac remodeling is still unclear. Objective To observe the effect of SF on cardiac remodeling in mice with high fat diet. Methods The research period was from August 2023 to June 2024. Twenty-one 8-week-old male C57BL/6J mice were randomly divided into the high-fat sleep fragmentation group（SF group，n=10） and the high-fat control group（Ctrl group，n=11）. They were placed in the sleep deprivation apparatus（XR-XS108） and the normal cage respectively. Both groups were given 45% high-fat feed，and the sleep fragmentation intervention lasted for 5 months. The degree of cardiac hypertrophy was evaluated by heart weight/body weight（HW/BW） and heart weight/tibia length（HW/TL）. The changes in cardiac structure were evaluated by echocardiography. Myocardial HE staining，Masson staining，and WGA staining were used to observe the size of myocardial cells and collagen content. The heart tissues of mice were sequenced for transcriptomics and metabolomics and the results were analyzed. Results Compared with the Ctrl group，the heart weight of the SF group increased（P<0.05），HW/BW and HW/TL rose（P<0.05），left ventricular internal dimension diastole，left ventricular internal dimension in systole，left ventricular end-diastolic volume，left ventricular end-systolic volumes all increased（P<0.05），and the left ventricular posterior wall thickness during diastole decreased（P<0.05）. HE staining showed that compared with the Ctrl group，the heart of the SF group was enlarged and the cardiomyocytes were enlarged；the statistical graph of Masson staining showed that compared with the Ctrl group，the myocardial fibrosis of the SF group increased（P<0.01）；the statistical graph of WGA staining showed that compared with the Ctrl group，the cardiomyocytes of the SF group were enlarged（P<0.001）. The transcriptomics results suggested that the TGF-β signaling pathway in the SF group was upregulated. Metabolomics suggested that the increase in cardiac remodeling in the SF group was related to the downregulation of glycerophospholipid metabolism pathways. Conclusion Sleep fragmentation can lead to cardiac enlargement，ventricular dilation，ventricular wall thinning，increased collagen content，and cardiac remodeling in mice with a high-fat diet. The mechanism may be related to up-regulation of TGF-β signaling pathway and down-regulation of glycerophospholipid metabolism.

Key words: Sleep fragmentation, High-fat diet, Cardiac remodeling, Transcriptomics, Metabolomics

摘要： 背景 睡眠片段化（SF）作为睡眠障碍的标志之一，对于心脏重塑的作用机制尚不明确。目的 观察SF对高脂饮食小鼠心脏重塑的作用。方法 研究时间为2023年8月—2024年6月。将21只8周龄C57BL/6J雄鼠随机分为高脂睡眠片段化组（SF组，n=10）与高脂对照组（Ctrl组，n=11），分别放置于睡眠剥夺仪（XR-XS108型）中和普通笼位中，两组均给予45%高脂饲料，睡眠片段化干预时间为5个月。以心脏/体质量（HW/BW）和心脏/胫骨长度（HW/TL）评价心脏肥大程度。以超声心动图评价心脏结构变化。采用心肌HE染色、Masson染色、WGA染色观察心肌细胞大小与胶原含量，获取小鼠的心脏组织进行转录组与代谢组学测序并分析结果。结果 与Ctrl组相比，SF组心脏重量增加（P<0.05），HW/BW与HW/TL升高（P<0.05），左心室舒张期内径、左心室收缩期内径、左心室舒张末期容积、左心室收缩末期容积增加（P<0.05），舒张期左心室后壁厚度下降（P<0.05）。HE染色显示，与Ctrl组相比，SF组心脏增大，心肌细胞增大；Masson染色统计图显示，与Ctrl组相比，SF组心肌纤维化增多（P<0.01）；WGA染色统计图显示，与Ctrl组相比，SF组心肌细胞增大（P<0.001）。转录组学结果提示SF组转化生长因子β（TGF-β）信号通路上调。代谢组学提示SF组心脏重塑增加与甘油磷脂代谢途径下调有关。结论 睡眠片段化能引起高脂饮食小鼠心脏增大，心腔增大，室壁变薄，胶原含量增多，造成心脏重塑增加。其机制可能与TGF-β信号通路上调，甘油磷脂代谢下调有关。

关键词: 睡眠片段化, 高脂饮食, 心脏重塑, 转录组学, 代谢组学