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OA
Astragaloside Ⅳ alleviates D-galactose-induced cardiomyocytes senescence and apoptosis by inhibiting the STING pathway
[目的]探讨黄芪甲苷(AS-Ⅳ)对D-半乳糖(D-gal)诱导的心肌细胞衰老的保护作用及其潜在机制.[方法]以心肌细胞H9C2为模型,采用D-gal诱导心肌细胞衰老,通过CCK-8法检测细胞活力,β-半乳糖苷酶(SA-β-Gal)染色评估细胞衰老程度,ROS检测细胞内活性氧水平,TUNEL检测细胞凋亡程度,qRT-PCR和Western blot检测衰老相关基因和蛋白(p21、p53)及干扰素基因刺激因子(STING)通路关键基因(STING、CXCL10和 MX-1)和蛋白(STING、cGAS、p-IRF3/IRF3)的表达水平.[结果]50 g/L D-gal显著降低心肌细胞活力,增加SA-β-Gal阳性率、细胞凋亡率和细胞内活性氧水平,并上调p16、p21及STING、cGAS、p-IRF3/IRF3通路蛋白表达(P<0.05);200 μmol/L AS-Ⅳ干预后,细胞活力显著增强,SA-β-Gal阳性率下降,细胞内活性氧水平降低,氧化应激损伤减轻,心肌细胞凋亡被抑制,衰老相关p21、p53的mRNA及蛋白水平下调(P<0.05).进一步对STING通路相关分子进行检测,qRT-PCR和Western blot结果显示 200 μmol/L AS-Ⅳ可抑制D-gal诱导的STING的mRNA和蛋白表达,降低p-IRF3/IRF3的蛋白表达水平.而SA-β-Gal阳性率、细胞内活性氧水平、DNA损伤结果和Western blot结果提示,STING激动剂(STING agonist-7)能够逆转AS-Ⅳ对D-gal诱导的心肌细胞衰老的改善效果.[结论]AS-Ⅳ可通过抑制STING通路激活,减轻D-gal诱导的心肌细胞衰老,为心血管衰老相关疾病的防治提供新策略.
[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.
郭文玉;高佳佳;段玮丽;阮焕钧;黄于朗;王珂妹;柯晓
中国医学科学院阜外医院深圳医院心内科,广东 深圳 518057中国医学科学院阜外医院深圳医院心内科,广东 深圳 518057中国医学科学院阜外医院深圳医院心内科,广东 深圳 518057中国医学科学院阜外医院深圳医院心内科,广东 深圳 518057深圳市前海蛇口自贸区医院心内科,广东 深圳 518067中国医学科学院阜外医院深圳医院心内科,广东 深圳 518057中国医学科学院阜外医院深圳医院心内科,广东 深圳 518057
医药卫生
黄芪甲苷D-半乳糖STING通路心肌细胞衰老
Astragaloside ⅣD-galactoseSTING pathwaycardiomyocytessenescence
《中山大学学报（医学科学版）》 2026 (1)
133-142,10
广东省自然科学基金面上项目(2021A1515010178)深圳市科技计划项目(JCYJ20220531091611026,JCYJ20230807150803007)深圳市南山区卫生科技计划项目(NSZD2025027)
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