[目的]探究环磷酸鸟苷-腺苷酸合成酶/干扰素刺激基因(cGAS-STING)信号通路在急性心肌梗死(AMI)小鼠模型中表达及作用。[方法]选择10～12周龄C57野生型小鼠，分为假手术组(只穿线不结扎)、模型组(结扎冠脉左降前支建立AMI小鼠模型)、STING抑制组(建模+腹腔注射5 mg/kg STING抑制剂C18)各10只，采用超声评估其心功能，HE染色、TUNEL法评估心肌组织病理情况及细胞凋亡，ELISA法检测血清炎性因子表达，Western Blot检测心肌组织cGAS、STING、IRF3及p-IRF3蛋白表达。[结果]与假手术组比较，模型组LVESD、LVEDD、心脏重量、左心室重量及其重量指数、心肌细胞凋亡率、血清TGF-β、1L-6、IL-18水平、心肌组织cGAS、STING、p-IRF3/IRF3蛋白表达明显升高，心脏梗死面积扩大，LVFS、LVEF下降;与模型组比较，STING抑制组LVEF、LVFS升高，LVESD、LVEDD、心脏重量、左心室重量及其重量指数、心肌细胞凋亡率、血清TGF-β、IL-6、IL-18水平、心肌组织cGAS(1。99±0。12 vs 0。73±0。09)、STING(1。41±0。18 vs 0。37±0。12)、p-IRF3/IRF3 蛋白表达降低，梗死面积减少(P＜0。05)。[结论]阻断cGAS-STING信号通路能改善AMI小鼠心功能，其机制可能与能减少心肌细胞凋亡和心室重构有关。
Expression and role of cGAS-STING signaling pathway related proteins in mouse model of acute myocardial infarction
[Objective]To explore the expression and role of Guanosine phosphate adenylate synthetase(cGAS)-stimulator of interferon genes(STING)signaling pathway related proteins in a mouse model of acute myocardial infarction(AMI).[Meth-od]The 10-or 12-week-old wild-type mice were selected,and classified into three groups,each with 10 rats.Rats in sham operation group were only threaded without ligation.In model group and STING inhibitor group,AMI model was induced by left anterior descending(LAD)coronary artery ligation.After model establishment,STING inhibitor group received intraperitoneal injection of a STING inhibitor(C18,5 mg/kg).The cardiac function was assessed by ultrasound.The changes in myocardial histopathology and myocardial fibrosis were observed by HE staining and TUNEL,expression levels of serum inflammatory fac-tors were detected by ELISA,and the protein expression levels of myocardial cGAS,STING,interferon regulatory factor 3(IRF3)and phospho-interferon regulatory factor 3(p-IRF3)were measured using Western Blotting.[Result]In comparison with sham operation group,model group had decreased left LVEF and LVFS,as well as increased LVESD,LVEDD,heart weight,left ventricular mass,left ventricular mass index,cardiac myocyte apoptosis rate,serum levels of transforming growth factor-β(TGF-β),interleukin-16(IL-16)and IL-18,and the protein expression levels of cGAS,STING,and p-IRF3/IRF3 in myocardial tissue.Compared with model group,STING inhibitor group had larger LVEF and LVFS,smaller LVESD and LVEDD,decreased heart weight,left ventricular mass,left ventricular mass index and cardiac myocyte apoptosis rate,lower ser-um levels of TGF-β,IL-6 and IL-18,and down-regulated protein expression levels of cGAS(1.99±0.12 vs 0.73±0.09),STING(1.41±0.18 vs 0.37±0.12)and p-IRF3/IRF3 in myocardial tissue,as well as less infarct size,with statisti-cal difference(all P＜0.05).[Conclusion]Blocking cGAS-STING signaling pathway can improve cardiac function,and its mechanism may be related to the the reduction of myocardial cell apoptosis and ventricular remodeling.
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