海南医科大学学报2025，Vol.31Issue(3)：178-184,7.DOI:10.13210/j.cnki.jhmu.20240910.001
抑制cGAS-STING信号通路对心肌缺血再灌注损伤小鼠巨噬细胞极化的影响
Effect of inhibiting cGAS-STING signaling pathway on macrophage polarization in mice undergoing myocardial ischemia-reperfusion injury
摘要
Abstract
Objective:To investigate the regulation of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)signal pathway on macrophage polarization in an animal model of myocardial isch-emia-reperfusion injury(MIRI).Methods:A total of 40 healthy male C57BL/6 mice were randomly divided into the control group,the sham group,the model group,and the RU.521(cGAS inhibitor)group,with 10 mice in each group.The model of MIRI was constructed in the model group and RU.521 group,the sham group had only thoracotomy but no coronary ligation,and the control group had no surgical procedure.The RU.521 group was intraperitoneally injected at a dose of 5 mg/kg/d,and the re-maining three groups were injected with an equal volume of 0.9%sodium chloride injection for 7 d.At the end of the experiment,myocardial tissue and serum samples were collected,the expression of cGAS and STING proteins was detected by Western blot(WB),the proportion of M1 and M2 macrophages was determined by flow cytometry,and the contents of IL-6,TNF-α,IL-10 and TGF-β were detected by enzyme-linked immunosorbent assay.Results:Compared to the control group and sham group,the expression levels of cGAS and STING proteins,the proportion of M1 macrophages,and the contents of IL-6 and TNF-α were significantly increased,but the proportion of M2 macrophages and the levels of IL-10 and TGF-β were significantly decreased in model group(P<0.001);Compared to the model group,the levels of GAS and STING protein expression,the proportion of M1 macrophages,and the contents of IL-6 and TNF-α were significantly decreased,but the proportion of M2 macrophages and the levels of IL-10 and TGF-β were significantly increased in the RU.521 group(P<0.01).Conclusion:Ischemia-reperfusion trig-gers activation of the cGAS-STING signaling pathway to promote the polarization of macrophages towards type M1 and enhance the inflammatory response.However,inhibition of this signaling pathway contributes to the polarization of macrophages towards type M2,which can limit the overactivated inflammatory response.关键词
cGAS-STING信号通路/急性心肌梗死/心肌缺血再灌注损伤/巨噬细胞Key words
cGAS-STING signal pathway/Acute myocardial infarction/Myocardial ischemia-reperfusion injury/Macro-phage分类
医药卫生引用本文复制引用
张焕鑫,沈祥礼,葛振嵘,王潇,宋涛,姜述斌..抑制cGAS-STING信号通路对心肌缺血再灌注损伤小鼠巨噬细胞极化的影响[J].海南医科大学学报,2025,31(3):178-184,7.基金项目
This study was supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region(2023D01C138) 新疆维吾尔自治区自然科学基金项目(2023D01C138) （2023D01C138）
