Study on the protective mechanism of resveratrol involved in sepsis-induced cardiomyopathy through activation of Sirt1/PGC-1α/Nrf2 pathway mediated by pyroptosis
10.3760/cma.j.cn114656-20241021-00735
- VernacularTitle:白藜芦醇通过激动Sirt1/PGC-1α/Nrf2通路介导的细胞焦亡参与脓毒性心肌病的保护作用机制研究
- Author:
Tong REN
1
;
Aizezi YIERZHATI
;
Yi WANG
;
Qindan QIN
;
Xiangyou YU
Author Information
1. 新疆医科大学第一附属医院重症医学中心，乌鲁木齐 830054
- Keywords:
Sepsis-induced cardiomyopathy;
Pyroptosis;
Sirt1;
PGC-1α;
Nrf2;
Resveratrol
- From:
Chinese Journal of Emergency Medicine
2025;34(7):945-952
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The aim of this study was to investigate the mechanism of resveratrol activation of Sirt1/PGC-1α/Nrf2 pathway and its protective effect on apoptosis in rats with sepsis cardiomyopathy.Methods:In this study, 32 SD male rats were randomly (random number) divided into sham operation group (sham group), sepsis group (C group), Sirt1 agonist group (S group), Sirt1 agonist +PGC-1α inhibitor group (SP group), and cecal exploration was performed in rats of Sham group. The other three groups underwent Cecal ligation and puncture (CLP) to establish a rat model of septic cardiomyopathy, and the corresponding groups were given Sirt1 agonist resveratrol and PGC-1α inhibitor SR-18292. The heart of the rats were examined by B ultrasound 20 hours after CLP to compare left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and left ventricular fraction shortening rate (LVFS). Myocardial tissue was stained with HE to observe the pathological changes, and serum myocardial troponin I (cTnI), interleukin-1β (IL-1β), interleukin-18 (IL-18) and oxidative stress indexes such as ROS and MDA were detected by ELISA. The expression levels of Sirt1, PGC-1α, Nrf2 and pyro related proteins (GSDMD, Caspase-1, NLRP3) in myocardial tissue were detected by Immunohistochemistry and Western Blotting.Results:Immunohistochemical and Western Blotting experiments showed that compared with sham group, the protein expressions of Sirt1, PGC-1α and Nrf2 in C group were decreased ( P < 0.05), and the expressions of GSDMD, Caspase-1 and NLRP3 were increased. The LVEF of group S rats was higher than that of group C rats ( P<0.05); Although the LVEDV and LVFS of group S were higher and the LVESV was lower, there was no statistically significant difference ( P > 0.05). Compared with group C, the edema and necrosis of cardiomyocytes in group S were alleviated, the arrangement of cardiomyocytes was slightly regular, and the inflammatory infiltration was reduced by HE staining. The cTnI, IL-1 β, IL-18, MDA, and ROS levels in group S were lower than those in group C ( P<0.05). Immunohistochemical and Western Blotting experiments showed that compared with group C, the protein expressions of Sirt1, PGC-1α and Nrf2 in group S were increased ( P < 0.05), and the expressions of GSDMD, Caspase-1 and NLRP3 were decreased ( P < 0.05). The LVESV of the SP group was higher than that of the S group rats ( P<0.05), while LVEDV, LVFS, and LVEF were all lower ( P>0.05). HE staining showed that the edema and necrosis of cardiomyocytes in SP group were more severe than those in S group, the arrangement of cardiomyocytes was more disordered than that in the former group, the vacuol-like deformation of cardiomyocytes was increased, and the infiltration of interstitial inflammatory cells was increased. The cTnI, IL-1 β, IL-18, MDA, and ROS levels in the SP group were higher than those in the S group rats ( P<0.05). There was no significant difference in Sirt1 expression between the SP group and the S group in myocardial tissue detected by immunohistochemistry and Western Blot. However, the expression levels of PGC-1 α and Nrf2 were lower in the SP group, while the expression levels of NLRP3, GSDMD, and Caspase-1 were higher in the SP group (all P<0.05). Conclusion:Resveratrol enhances myocardial function and decreases inflammatory cytokine levels in rats suffering from septic cardiomyopathy, potentially through a mechanism involving the Sirt1/PGC-1α/Nrf2 pathway.
