中山大学学报（医学科学版）2026，Vol.47Issue(1)：133-142,10.DOI:10.11714/jsysu.med.YX20250094
黄芪甲苷通过抑制STING通路减轻D-半乳糖诱导的心肌细胞衰老和凋亡
Astragaloside Ⅳ alleviates D-galactose-induced cardiomyocytes senescence and apoptosis by inhibiting the STING pathway
摘要
Abstract
[Objective]To investigate the protective effect of Astragaloside Ⅳ(AS-Ⅳ)on D-galactose(D-gal)-induced cardiomyocytes senescence and its potential mechanisms.[Methods]Using H9C2 cardiomyocytes as a model,D-gal was used to induce cardiomyocyte senescence.Cell viability was assessed using the CCK-8 assay,senescenceextent was evaluated via β-galactosidase(SA-β-Gal)staining,reactive oxygen species(ROS)levels were measured to assess intracellular oxidative stress,apoptosis extent was determined using the TUNEL assay,and qRT-PCR and Western blot analyses were conducted to examine the expression levels of senescence-related genes and proteins(p21、p53)and key genes(STING,CXCL10,and MX-1)and proteins(STING,cGAS,p-IRF3/IRF3)of the stimulator of interferon genes(STING)pathway.[Results]The 50 g/L D-gal significantly reduced myocardial cell viability,increased SA-β-Gal positivity,apoptosis rate,and intracellular reactive oxygen species levels,and upregulated the expression of p16,p21,and STING,cGAS,p-IRF3/IRF3 pathway proteins(P<0.05);After intervention with 200 μmol/L of AS-Ⅳ,cell viability was significantly enhanced,the SA-β-Gal-positive rate decreased,intracellular reactive oxygen species levels decreased,oxidative stress damage was alleviated,myocardial cell apoptosis was inhibited,and the mRNA and protein levels of aging-related p21 and p53 were downregulated(P＜0.05).Further detection of STING pathway-related molecules showed that 200 μmol/L of AS-IV inhibited D-galactose-induced STING mRNA and protein expression and reduced p-IRF3/IRF3 protein expression levels,as demonstrated by qRT-PCR and Western blot results.However,the SA-β-Gal positivity rate,intracellular reactive oxygen species(ROS)levels,DNA damage results,and Western blot findings suggested that the STING agonist(STING agonist-7)could reverse the ameliorative effects of AS-Ⅳ on D-galactose-induced cardiomyocytes senescence.[Conclusion]AS-Ⅳ may mitigate D-gal-induced cardiomyocytes senescence by inhibiting STING pathway activation,providinga new strategy for the prevention and treatment of cardiovascular senescence-related diseases.关键词
黄芪甲苷/D-半乳糖/STING通路/心肌细胞/衰老Key words
Astragaloside Ⅳ/D-galactose/STING pathway/cardiomyocytes/senescence分类
医药卫生引用本文复制引用
郭文玉,高佳佳,段玮丽,阮焕钧,黄于朗,王珂妹,柯晓..黄芪甲苷通过抑制STING通路减轻D-半乳糖诱导的心肌细胞衰老和凋亡[J].中山大学学报（医学科学版）,2026,47(1):133-142,10.基金项目
广东省自然科学基金面上项目(2021A1515010178) （2021A1515010178）
深圳市科技计划项目(JCYJ20220531091611026,JCYJ20230807150803007) （JCYJ20220531091611026,JCYJ20230807150803007）
深圳市南山区卫生科技计划项目(NSZD2025027) （NSZD2025027）
