cGAS-STING通路在劳力性热射病所致心肌损伤中的作用研究  

Research on the Role of cGAS-STING Pathway in Exertional Heat Stroke-Induced Myocardial Injury

作　　者：刘诗杰 饶志坚[1,2] 黄鹏 耿雪 吴东哲 瞿超艺 魏强嫚 赵杰修 LIU Shijie;RAO Zhijian;HUANG Peng;GENG Xue;WU Dongzhe;QU Chaoyi;WEI Qiangman;ZHAO Jiexiu(China Institute of Sport Science,Beijing 100061,China;Shanghai Normal University,Shanghai 201418,China;Shanghai University of Sport,Shanghai 200438,China;Beijing Sport University,Beijing 100084,China;Hebei Normal University,Shijiazhuang 050024,China)

机构地区：[1]国家体育总局体育科学研究所,北京100061 [2]上海师范大学,上海201418 [3]上海体育大学,上海200438 [4]北京体育大学,北京100084 [5]河北师范大学,河北石家庄050024

出　　处：《体育科学》2024年第4期80-88,共9页China Sport Science

基　　金：国家自然科学基金面上项目(31371195);国家体育总局体育科学研究所基本科研业务费资助项目(基本23-48);国家重点研发计划项目(2019YFF0301600)。

摘　　要：目的:探讨cGAS-STING通路在劳力性热射病(exertional heat stroke,EHS)所致心肌炎症中的作用。方法:将8周龄C57BL/6N雄性小鼠随机分为安静对照组(C组)、劳力性热射病发病即刻组(EHS0组)、劳力性热射病发病3天组(EHS3组)和劳力性热射病发病14天组(EHS14组)。发病组在温度为37.5℃±1℃、湿度为45%±5%的高温舱中进行力竭跑台运动,构建EHS小鼠模型。采用心动超声仪检测小鼠心功能指标,苏木精-伊红(HE)染色观察小鼠心肌组织病理变化,ELISA测定血清IL-6与cTnI水平,qPCR检测心肌组织cGAS、STING、IRF3、NF-κB、γH2AX、IL-6、TFAM、PGC-1αmRNA相对表达量,透射电镜观察小鼠心肌线粒体超微结构变化,Western blot检测心肌组织cGAS、p-NF-κB p65、γH2AX蛋白表达水平。结果:1)与C组比较,EHS组小鼠的心动超声指标(LVAWd、LVAWs、LVPWd、LVPWs、LVIDd和LVIDs)显著增加,LVEF和LVFS显著下降,心肌细胞出现肥大,肌纤维排列紊乱,伴有炎症细胞浸润,心肌线粒体固缩破裂,线粒体嵴溶解出现空泡改变,内部基质密度分布不均匀,Z线模糊,大量肌丝溶解断裂,且EHS发病后14天仍未完全恢复。2)EHS组小鼠的血清IL-6、cTnI水平和心肌组织NF-κB、PGC-1α、TFAM、cGAS、IRF3 mRNA表达量及cGAS、p-NF-κB p65、γH2AX蛋白表达水平均显著升高,EHS发病后14天基本恢复。结论:1)EHS发病后可引起小鼠心肌炎症反应,其机制可能与cGAS-STING信号通路的激活有关。2)EHS后心脏长期功能障碍与血清IL-6和cTnI的水平无关,而可能与心肌纤维紊乱、细胞肥大、心肌线粒体形态结构改变等有关。Objective:To investigate the role of the cGAS-STING pathway in myocardial inflammation induced by exertional heat stroke(EHS).Methods:Eight-week-old male C57BL/6N mice were randomly divided into a sedentary control group(C group),an exertional heat stroke immediate group(EHS0 group),an exertional heat stroke 3 days group(EHS3 group),and an exertional heat stroke 14 days group(EHS14 group).The EHS model was established by subjecting the mice in the EHS groups to exhaustive treadmill exercise in a high-temperature chamber set at 37.5℃±1℃with 45%±5%humidity.Cardiac function was assessed using echocardiography.Histopathological changes in myocardial tissue were observed with hematoxylin-eosin(HE)staining.Serum IL-6 and cTnI levels were measured by ELISA.The relative mRNA expression levels of cGAS,STING,IRF3,NF-κB,γH2AX,IL-6,TFAM and PGC-1αin myocardial tissue were detected by qPCR.Mitochondrial ultrastructure changes in myocardial tissue were examined by transmission electron microscopy.The protein expression levels of cGAS,p-NF-κB p65 andγH2AX in myocardial tissue were determined by Western blot.Results:1)Compared with the C group,the EHS groups showed significantly increased echocardiographic indices(LVAWd,LVAWs,LVPWd,LVPWs,LVIDd,and LVIDs)and significantly decreased LVEF and LVFS.Myocardial cells exhibited hypertrophy,disorganized muscle fibers,and inflammatory cell infiltration.Mitochondrial contraction,rupture,cristae dissolution with vacuolation,uneven distribution of internal matrix density,blurred Z-lines,and extensive myofilament dissolution and breakage were observed.These changes persisted 14 days post-EHS.2)serum levels of IL-6 and cTnI,and the mRNA expression levels of NF-κB,PGC-1α,TFAM,cGAS and IRF3,as well as the protein expression levels of cGAS,p-NF-κB p65 andγH2AX in myocardial tissue,were significantly elevated in the EHS groups and generally recovered by 14 days post-EHS.Conclusions:1)EHS induces myocardial inflammatory responses in mice,potentially through the activation of the cGA

关 键 词：劳力性热射病 心肌炎症 cGAS-STING信号通路 线粒体 

分 类 号：G804.2[文化科学—运动人体科学]