Effect of esketamine on caspase-11-mediated non-canonical pathway pyroptosis in sepsis-induced acute lung injury in rats
10.3760/cma.j.cn131073-20240929-00319
- VernacularTitle:艾司氯胺酮对脓毒症大鼠急性肺损伤时caspase-11介导的非经典途径细胞焦亡的影响
- Author:
Yunfei BAO
1
;
Zhihao FENG
;
Yanyan NIU
;
Qing HU
;
Haijie LIU
;
Hongbo ZHANG
;
Jianling LI
Author Information
1. 承德医学院附属医院麻醉科 河北省泛血管疾病重点实验室，承德 067000
- Publication Type:Journal Article
- Keywords:
Sepsis;
Acute lung injury;
Caspases;
Pyroptosis;
Esketamine
- From:
Chinese Journal of Anesthesiology
2025;45(3):364-368
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of esketamine on caspase-11-mediated non-canonical pathway pyroptosis in sepsis-induced acute lung injury in rats.Methods:Eighteen SPF healthy Sprague-Dawley rats, aged 8-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+ esketamine group (CLP+ ES group). Sepsis was induced by CLP in anesthetized animals. Esketamine 10 mg/kg was injected via the tail vein immediately after development of the model, and the equal volume of normal saline was injected via the tail vein in the other two groups. At 24 h after development of the model, the rats were sacrificed under anesthesia, and the lung tissues and blood samples were taken. The wet to dry lung weight ratio (W/D ratio) was calculated, and the pathological changes were observed and the lung injury was scored. The expression of caspase-11, gasdermin D-N (GSDMD-N), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) was detected by Western blot. The expression of caspase-11 and GSDMD-N mRNA was detected by quantitative real-time polymerase chain reaction. The serum concentration of interleukin-1β (IL-1β) was determined by enzyme-linked immunosorbent assay. Results:Compared with Sham group, the lung injury score and W/D ratio were significantly increased, the expression of caspase-11 and GSDMD-N protein and mRNA was up-regulated, the expression of p-PI3K and p-AKT was down-regulated, and the concentration of IL-1β was increased in CLP group ( P<0.05). Compared with CLP group, the lung injury score and W/D ratio were significantly decreased, the expression of caspase-11 and GSDMD-N protein and mRNA was down-regulated, the expression of p-PI3K and p-AKT was up-regulated, and the concentration of IL-1β was decreased in CLP+ ES group ( P<0.05). Conclusions:The mechanism by which esketamine alleviates sepsis-induced acute lung injury may be related to the inhibition of caspase-11-mediated non-canonical pathway pyroptosis in rats.
