南京农业大学学报2025，Vol.48Issue(2)：410-418,9.DOI:10.7685/jnau.202403007
干扰素基因刺激因子在金黄色葡萄球菌感染引起粒体功能障碍中的作用研究
Effects of STING in the mitochondrial dysfunction induced by Staphylococcus aureus infection
摘要
Abstract
[Objectives]This study aimed to investigate the impact of stimulator of interferon gene(STING)on mitochondrial dysfunction caused by Staphylococcus aureus infection,providing theoretical support for the prevention and control of S.aureus-induced mastitis.[Methods]The study utilized the mouse mammary epithelial cell line(EpH4-Ev)and S.aureus(ATCC 29213)as research models,and organized into three cell experiment groups:the control group(including treatment with STING inhibitor C-176 alone,mitochondrial division inhibitor Mdivi-1 alone or nothing),the infection group(exposed to S.aureus),and the treatment group(C-176+S.aureus and Mdivi-1+S.aureus).The activation of STING pathway,expression levels of mitochondria-related proteins,mtDNA,mROS,MMP,and mitochondrial morphology alterations in mammary epithelial cells were detected respectively.Animal experiments conducted on wild-type C57BL/6(WT)and STING knockout(ΔSTING)mice,divided into the control group(mice without treatment)and the infection group(WT treated with S.aureus and ΔSTING treated with S.aureus).T-AOC,NAGase,MDA and other biochemical indicators in liver and mammary glands were analyzed.[Results]S.aureus infection activated STING pathway,resulting in increased phosphorylation levels of DRP1 at Ser616(P<0.05),and decreased expression levels of MFN1 and MFN2(P<0.05).Both C-176 and Mdivi-1 reduced the phosphorylation level of DRP1 at Ser616(P<0.01),restored expression of MFN1 and MFN2(P<0.05),and alleviated mitochondrial fragmentation caused by S.aureus infection.Furthermore,treatment with both C-176 and Mdivi-1 significantly inhibited the elevation in mROS levels and the decrease in MMP(P<0.05)induced by S.aureus infection,as well as the decrease in mtDNA copy number(P<0.05).In addition,STING gene deletion restored T-AOC levels in liver and mammary glands of S.aureus-infected mice(P<0.01),and reduced NAGase activity and MDA level(P<0.05).[Conclusions]Inhibiting STING can improve mitochondrial dysfunction induced by S.aureus infection in mammary epithelial cells,and deletion of STING gene can alleviate tissue damage and oxidative stress caused by S.aureus infection in liver and mammary glands.关键词
奶牛乳腺炎/金黄色葡萄球菌/干扰素基因刺激因子/线粒体功能障碍Key words
bovine mastitis/S.aureus/stimulator of interferon gene(STING)/mitochondrial dysfunction分类
农业科技引用本文复制引用
吴斌凤,高兴,孙乃岩,仇亚伟,张金秋,苗晋锋..干扰素基因刺激因子在金黄色葡萄球菌感染引起粒体功能障碍中的作用研究[J].南京农业大学学报,2025,48(2):410-418,9.基金项目
国家自然科学基金项目(32072867,32273013,32172895) （32072867,32273013,32172895）
