首页|期刊导航|中国全科医学|睡眠片段化对高脂喂养小鼠心脏重塑的作用研究

睡眠片段化对高脂喂养小鼠心脏重塑的作用研究OA

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

中文摘要英文摘要

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.

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.

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100034 北京市,北京大学第一医院内分泌科100034 北京市,北京大学第一医院内分泌科100034 北京市,北京大学第一医院内分泌科100034 北京市,北京大学第一医院内分泌科

医药卫生

睡眠片段化高脂饮食心脏重塑转录组学代谢组学

Sleep fragmentationHigh-fat dietCardiac remodelingTranscriptomicsMetabolomics

《中国全科医学》 2026 (23)

3329-3335,3341,8

国家自然科学基金青年项目(82101554)

10.12114/j.issn.1007-9572.2025.0002

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