Research on the Role of cGAS-STING Pathway in Exertional Heat Stroke-Induced Myocardial Injury
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-1α in 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 and γH2AX 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 and γH2AX 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 cGAS-STING signaling pathway.2)long-term cardiac dysfunction post-EHS is not associated with serum IL-6 and cTnI levels but may be related to disorganized myocardial fibers,cell hypertrophy,and structural changes in myocardial mitochondria.
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