摘要
目的:应激诱导蛋白2(Sestrin2)作为应激诱导的结构蛋白,在参与维持心肌供能及代谢平衡、保护细胞防御应激损伤方面具有重要作用。通过考查有氧运动通过调节心肌Sestrin2特异性表达对下游的心肌代谢敏感信号通路AMPK-PGC-1α产生的影响,揭示该信号通路对代谢的影响及其对脂毒性心肌产生保护作用的机制。方法:雄性C57BL/6小鼠制备高脂饮食诱导建立肥胖小鼠模型并实施有氧运动,WGA染色法及超声心动图法评价有氧运动对心肌重建及心功能指标的影响;采用外源性Sestrin2干预H9C2细胞评价离体心肌细胞AMPK-PGC-1α调控对损伤、炎症的作用。结果:有氧运动负荷能够显著抑制HFD小鼠心肌细胞肥大、炎症因子指标的上升,进而保护心肌细胞及心室功能。外源性Sestrin2干预可激活AMPK-PGC-1α信号通路,缓解离体心肌细胞损伤和炎症指标。结论:Sestrin2激活AMPK-PGC-1α信号通路是缓解脂毒性心肌炎症及损伤的重要机制,有氧运动可通过上调Sestrin2经AMPK-PGC-1α信号通路抑制心肌炎症因子,提高肽类激素mRNA水平,起到防御脂毒性心肌损伤的作用。
Objective:Sestrin2,as a stress-induced structural protein,plays an important role in maintaining myocardial energy supply and metabolic balance,and protecting cells from stress damage.For investigating the effect of aerobic exercise and relative specific expression of Sestrin2 on the AMPK-PGC-1αwhich is the myocardial metabolism sensitive signaling pathway,we focus on the impact of this pathway on metabolism and its protective mechanism against lipid toxicity in myocardium.Methods:Male C57BL/6 mice were induced to establish an obese mouse model by high-fat diet,and aerobic exercise was performed.The effects of aerobic exercise on myocardial reconstruction and cardiac function indicators were evaluated by WGA staining and echocardiography;using exogenous Sestrin2 intervention on H9C2 cells,we evaluate the effect of AMPK-PGC-1αregulation on injury and inflammation in isolated cardiomyocytes.Results:Aerobic exercise loading can significantly inhibit cardiomyocyte hypertrophy in HFD mice,suppress the increase of inflammatory cytokine indicators,and thus protect cardiomyocyte and ventricular function.Exogenous Sestrin2 intervention can activate the AMPK-PGC-1αpathway,alleviate ex vivo myocardial cell damage and inflammatory markers.Conclusions:Activation of the AMPK-PGC-1αsignaling pathway by Sestrin2 is an important mechanism for alleviating lipotoxic myocarditis and injury.Aerobic exercise inhibited myocarditis cytokines by upregulating Sestrin2 through the AMPK-PGC-1αpathway,increase peptide hormone mRNA levels,and play a role in defending against lipotoxic myocardial injury.
作者
赵文辉
王蕾
焦瀚仪
王杨
ZHAO Wenhui;WANG Lei;JIAO Hanyi;WANG Yang(Changzhi University,Changzhi 046011,China;Changzhi Medical College,Changzhi 046000,China;Hainan Medical University,Haikou 571109,China)
出处
《中国体育科技》
北大核心
2025年第1期59-67,共9页
China Sport Science and Technology
基金
海南省重点研发计划项目(ZDYF2017121)
海南省科协青年科技英才创新计划项目(QCXM201920)。
