NR4A1 ameliorates the inflammation of postoperative ileus through inhibiting p38MAPK/ NF-κB pathway
10.3760/cma.j.issn.1671-0282.2025.06.011
- VernacularTitle:NR4A1通过抑制p38MAPK/NF-κB信号通路改善术后肠梗阻的作用机制
- Author:
Xinchang SHANGGUAN
1
;
Jin YE
;
Xianqiang CHEN
;
Junrong ZHANG
;
Jiawen LIU
;
Yong WEI
Author Information
1. 福建医科大学附属协和医院急诊外科，福州 350001
- Keywords:
NR4A1;
p38MAPK;
NF-κB;
Postoperative ileus;
Inflammatory response;
Intestinal propulsive rate;
Intestinal mucosal barrier;
Cell apoptosis
- From:
Chinese Journal of Emergency Medicine
2025;34(6):811-818
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To examine the therapeutic effects and molecular mechanisms of nuclear receptor NR4A1 in alleviating postoperative ileus (POI) in a rat model.Methods:Twenty-four Sprague-Dawley rats were randomly(random number) divided into four groups ( n=6/group): sham-operated control, POI model, POI model + NR4A1 stimultior (Cytosporone B, 13 mg/kg), and POI model + NR4A1 antagonist (DIM-C-pPhCO2Me, 2 mg/kg). After 24 hours, intestinal tissues and serum were collected for analysis. We assessed: (1) histopathological changes, (2) intestinal motility via propulsion rate, (3) NR4A1 expression by immunohistochemistry, (4) epithelial apoptosis via TUNEL assay, (5) inflammatory cytokines (IL-6, IL-4) by ELISA, (6) tight junction protein (occludin) by Western blot, and (7) p38MAPK/NF-κB pathway activation through combined western blot and immunofluorescence analyses. Results:Compared with sham controls, POI model rats showed (all P<0.05): significantly reduced NR4A1 expression, severe mucosal damage, increased inflammatory infiltration, elevated epithelial apoptosis, decreased occludin expression, impaired intestinal motility, upregulated pro-inflammatory cytokines (IL-6, IL-4), and activated p38MAPK/NF-κB signaling. NR4A1 activation with Cytosporone B significantly reversed these pathological changes (all P<0.05), while NR4A1 inhibition exacerbated them. Conclusions:NR4A1 activation attenuates POI by suppressing p38MAPK/NF-κB-mediated inflammation and preserving intestinal barrier function, suggesting its potential as a therapeutic target for postoperative ileus.
