Effects of daphnetin modulating STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats
- VernacularTitle:瑞香素调节STING/TBK1/IRF3信号通路对脓毒症大鼠免疫炎症反应的影响
- Author:
Ya WEN
1
;
Yan LI
1
;
Siyi BAI
1
;
Kailin CHEN
1
;
Liying CHENG
1
;
Yadong LI
1
Author Information
- Publication Type:Journal Article
- Keywords: daphnin; sepsis; cecal ligation puncture (CLP); STING/TBK1/IRF3 signaling pathway; immune regulation; inflammation
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):822-827
- CountryChina
- Language:Chinese
- Abstract: 【Objective】 To explore the effects of dapnetin’s regulation of STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats. 【Methods】 In this study, 80 male Sprague Dawley (SD) rats were selected and randomly divided into four groups, 20 rats in the sham-operation group, the remaining 60 mice with sepsis were constructed according to cecal ligation puncture (CLP) method and were intraperitoneally injected with different doses of dapnetin. They were divided into no-dapnetin model group (0 mg/kg), low-dose group (2.5 mg/kg), and high-dose group (5 mg/kg), with 20 mice in each group. The model group and sham-operation group were intraperitoneally injected with 0.1% DMSO. The survival rate of rats in each group after 72 h of CLP modeling was observed. Lung, kidney, liver and spleen tissues were collected for histopathological analysis. Serum inflammatory factors (TNF-α, IL-6, and IL-1β) were detected by ELISA, T lymphocyte subsets in peripheral blood were detected by flow cytometry, and STING/TBK1/IRF3 signaling pathway protein expression was detected by Western blotting. 【Results】 Compared with sham-operation group, the survival rate of rats in model group was reduced (P<0.05), each organ tissue injury was significant, serum inflammatory factors (TNF-α, IL-6, and IL-1β) levels were increased (P<0.05), CD4+ ratio and CD4+/CD8+ ratio in peripheral blood were decreased (P<0.05), while CD8+ ratio and Th1/Th2 ratio were increased (P<0.05), the protein expressions of STING, p-TBK1/TBK1 and p-IRF3/IRF3 were downregulated (P<0.05). Compared with the model group, dapnetin in high-dose group improved the survival rate of rats (P<0.05), the injury of all organs and tissues was reduced, and the level of serum inflammatory factors was decreased (P<0.05), CD4+ ratio and CD4+/CD8+ ratio in peripheral blood were increased (P<0.05), while CD8+ ratio and Th1/Th2 ratio were decreased (P<0.05), the protein expressions of STING, p-TBK1/TBK1 and p-IRF3/IRF3 were increased (P<0.05). 【Conclusion】 Dapnetin can improve the immune inflammatory response of sepsis rats by regulating STING/TBK1/IRF3 signaling pathway.
