睡眠片段化对高脂喂养小鼠心脏重塑的作用研究

doi:10.12114/j.issn.1007-9572.2025.0002

中国全科医学 ›› 2026, Vol. 29 ›› Issue (23): 3329-3335.DOI: 10.12114/j.issn.1007-9572.2025.0002

睡眠片段化对高脂喂养小鼠心脏重塑的作用研究

杨乐宁, 汪黎明, 赵晨旭, 李戈^*(), 高莹

100034　北京市，北京大学第一医院内分泌科

收稿日期:2025-01-06 修回日期:2025-03-18 出版日期:2026-08-15 发布日期:2026-07-03
通讯作者: 李戈
作者贡献：
杨乐宁参与进行研究设计，动物造模与组学实验的实施，数据统计与整理，撰写论文；汪黎明进行病理染色，部分数据的收集与整理；赵晨旭参与文章修改；李戈负责文章的质量控制与审查，对文章整体负责，监督管理；高莹负责文章的审核，校正与质量控制。
基金资助:
国家自然科学基金青年项目(82101554)

The Effect of Sleep Fragmentation on Cardiac Remodeling in High-fat Fed Mice

YANG Lening, WANG Liming, ZHAO Chenxu, LI Ge^*(), GAO Ying

Department of Endocrinology, Peking University First Hospital, Beijing 100034, China

Received:2025-01-06 Revised:2025-03-18 Published:2026-08-15 Online:2026-07-03
Contact: LI Ge

摘要/Abstract

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=11）与高脂对照组（Ctrl组，n=10），分别放置于睡眠剥夺仪和普通笼位中，两组均给予45%高脂饲料，睡眠片段化干预时间为5个月。以心脏质量/体质量（HW/BW）和心脏质量/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、小麦胚芽凝集素（WGA）染色观察心肌细胞大小与胶原含量，分离小鼠的心肌组织进行转录组与代谢组学测序并分析心脏重塑机制。结果与Ctrl组相比，SF组心脏质量增加（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

Abstract:

Background

Sleep fragmentation (SF) is one of the hallmarks of sleep disorders, and the mechanism 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=11) and the high-fat control group (Ctrl group, n=10). They were placed in the sleep deprivation apparatus 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 mechanism in cardiac remodeling was 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

中图分类号:

R 338.63　R 151.3

杨乐宁,汪黎明,赵晨旭,等. 睡眠片段化对高脂喂养小鼠心脏重塑的作用研究[J]. 中国全科医学, 2026, 29(23): 3329-3335. DOI: 10.12114/j.issn.1007-9572.2025.0002.
YANG Lening,WANG Liming,ZHAO Chenxu, et al. The Effect of Sleep Fragmentation on Cardiac Remodeling in High-fat Fed Mice[J]. Chinese General Practice, 2026, 29(23): 3329-3335. DOI: 10.12114/j.issn.1007-9572.2025.0002.

图/表 8

图1 两组小鼠体质量与心脏质量比较注：A为两组小鼠20周体质量变化；B为心脏大体图；C为两组小鼠心脏质量比较；D为心脏质量/胫骨长度（HW/TL）；E为心脏质量/体质量（HW/BW）；*为P<0.05，**为P<0.01；对照组（Ctrl组）10只小鼠，睡眠片段化组（SF组）11只小鼠。

Figure 1 Comparison of body weight and heart weight

图2 两组小鼠心脏超声结果比较注：A为左心室舒张期内径（LVIDd），B为左心室舒张末期容积（LVEDV），C为左心室收缩期内径（LVIDs），D为左心室收缩末期容积（LVESV），E为舒张期左心室后壁厚度（LVPWd），F为收缩期左心室后壁厚度（LVPWs），G为舒张期左心室前壁厚度（LVAWd），H为收缩期左心室前壁厚度（LVAWs）；*为P<0.05，**为P<0.01，ns为P>0.05；Ctrl组10只小鼠，SF组11只小鼠。

Figure 2 Comparison of cardiac ultrasound in two groups of mice

图3 心肌组织HE、Masson、WGA染色结果注：A分别为HE染色×20、×400，Masson染色×400，小麦胚芽凝集素（WGA）染色×400图像；B为Masson染色胶原面积统计图；C为WGA染色心肌细胞平均面积统计图；**为P<0.01，***为P<0.001；Ctrl组7只小鼠，SF组8只小鼠。

Figure 3 Comparison of HE，Masson and WGA staining results of heart tissues

图4 两组差异表达基因火山图和热图注：A为火山图，B为热图。

Figure 4 Volcano map and heatmap of differentially expressed genes in two groups

图5 两组差异表达基因GO与KEGG富集分析图注：BP=生物过程，CC=细胞组成，MF=分子功能；A为差异表达基因的GO富集分析，B为差异表达基因的KEGG富集分析。

Figure 5 GO and KEGG enrichment analysis diagram of differentially expressed genes in two groups

图6 GSEA图注：A为胶原纤维GSEA分析图，B为细胞外基质GSEA分析图，C为转化生长因子β通路GSEA分析图。

Figure 6 GSEA map

图7 代谢组学图注：A为主成分得分图，B为显著差异代谢物图，C为差异代谢物通路富集图。

Figure 7 Metabolomics map

图8 转录组学与代谢组学联合分析图注：红色虚线表示两者之间为正相关，灰色虚线表示两者之间为负相关，白色圆形标注为差异表达基因，黄色三角形标注为溶血磷脂差异代谢物，虚线上数字表示差异表达基因与差异代谢物的相关系数；A为所有差异表达基因与所有溶血磷脂差异代谢物之间的相关性全景网络图，B为Comp基因与各差异溶血磷脂代谢物的相关性放射状展示图，C为Col8a2基因与各差异溶血磷脂代谢物的相关性放射状展示图，D为NOX4基因与各差异溶血磷脂代谢物的相关性放射状展示图。

Figure 8 Combined transcriptomic and metabolomics analysis diagram

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睡眠片段化对高脂喂养小鼠心脏重塑的作用研究

The Effect of Sleep Fragmentation on Cardiac Remodeling in High-fat Fed Mice

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