Effect of irbesartan on hypoxia reoxygenation induced myocardial cell pyroptosis by regulating cGAS-STING signaling pathway
10.3969/j.issn.1000-484X.2025.11.010
- VernacularTitle:厄贝沙坦调节cGAS-STING信号通路对缺氧复氧诱导的心肌细胞焦亡的影响
- Author:
Lingling LIU
1
;
Yongjin YAN
1
;
Shiya WANG
1
;
Shunzhong GU
1
Author Information
1. 海安市人民医院心血管内科,南通 226600
- Publication Type:Journal Article
- Keywords:
Irbesartan;
cGAS-STING signaling pathway;
Hypoxia reoxygenation;
Pyroptosis
- From:
Chinese Journal of Immunology
2025;41(11):2613-2618
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of irbesartan on hypoxia reoxygenation(HR)induced myocardial cell pyropto-sis by regulating the cGAS-STING signaling pathway.Methods:H9c2 myocardial cells were cultured in vitro and grouped into control group,HR group,low-dose irbesartan group,high-dose irbesartan group,high-dose irbesartan+RocA(cGAS-STING signaling path-way activator)group,and RU.521(cGAS-STING signaling pathway inhibitor)group.Cell viability was detected by CCK-8;ELISA was applied to detect levels of lactate dehydrogenase(LDH),IL-6,IL-18 and IL-1β;propidium iodide(PI)staining method was applied to detect the formation of cell membrane pores;RT-qPCR method was applied to detect the expressions of cGAS and STING mRNA in cells;Western blot method was applied to detect the expressions of NLRP3,Caspase-1,GSDMD,cGAS and STING pro-teins.Results:Compared with the control group,the A450 values(24 h,48 h)of H9c2 cells in the HR group were obviously reduced,the levels of LDH,IL-6,IL-18,IL-1β,PI staining positive rate,the expressions of cGAS,STING mRNA,the expressions of NLRP3,Caspase-1,GSDMD,cGAS,STING proteins were obviously increased(P<0.05);compared with the HR group,the A450 values(24 h,48 h)of H9c2 cells in the low and high dose irbesartan groups and the RU.521 group were obviously increased,the levels of LDH,IL-6,IL-18,IL-1β,PI staining positive rate,the expressions of cGAS,STING mRNA,the expressions of NLRP3,Caspase-1,GSDMD,cGAS,STING proteins were obviously reduced(P<0.05);RocA was able to partially reverse the protective effect of irbe-sartan on HR-induced myocardial cells(P<0.05);the detection indicators of H9c2 cells in the RU.521 group were at the same level as those in the high-dose irbesartan group(P>0.05).Conclusion:Irbesartan can inhibit HR-induced myocardial cell pyrop-tosis by inhibi-ting the cGAS-STING signaling pathway.
