Related Experiment Video
Updated: Jul 16, 2026
A Rat Model of Pouchitis Following Proctocolectomy and Ileal Pouch-Anal Anastomosis Using Dextran Sulfate Sodium
Published on: May 31, 2024
Blockade of p38 mitogen-activated protein kinase pathway ameliorates delayed intestinal transit in burned rats
Hua Tian Gan1, Pankaj J Pasricha, Jiande D Z Chen
1Department of Geriatrics Medicine, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China.
Background:
Burn injury has been shown to impair intestinal transit. p38 mitogen-activated protein kinase (MAPK) has been shown to be involved in the production of proinflammatory mediators such as interleukin (IL)-1beta, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The aims of this study were to investigate the effects of SB203580, a specific p38 MAPK inhibitor, on intestinal transit and to elucidate its possible mechanism.
Methods:
Burn rats and sham rats were divided into 4 groups: saline, S-methylisothiourea (a selective iNOS inhibitor), nimesulide (a selective COX-2 inhibitor), or SB203580. Intestinal transit was measured using phenol red and assessed using the geometric center. The protein or gene expression of NOS, COX-2, and IL-1beta were measured by real-time reverse-transcription polymerase chain reaction or Western blot analysis. p38 MAPK activity or myeloperoxidase (MPO) activity was determined by using the p38 MAPK assay kit or MPO assay kit.
Results:
Intestinal transit was delayed significantly with burn injury, improved significantly with S-methylisothiourea and nimesulide, but almost completely normalized with SB203580. p38 MAPK activity, MPO activity, iNOS, COX-2, and IL-1beta protein or gene expression increased markedly after burn injury. SB203580 inhibited p38 MAPK and MPO activity, and reduced iNOS, COX-2, and IL-1beta protein or gene expression.
Conclusions:
Burn-induced delayed intestinal transit is associated with the p38 MAPK pathway. Inhibition of the p38 MAPK pathway ameliorates delayed intestinal transit, at least in part, by inhibiting iNOS, COX-2, and IL-1beta expression. Thus, p38 MAPK could represent a novel target for therapy of gut dysmotility after burn injury.
Insights
Burn injury delays intestinal transit, but inhibiting p38 MAPK with SB203580 normalizes this function. This occurs by reducing inflammatory mediators like iNOS, COX-2, and IL-1beta, suggesting p38 MAPK as a therapeutic target.
Area of Science:
- Gastroenterology
- Molecular Biology
- Burn Injury Research
Background:
- Burn injury significantly impairs intestinal transit.
- p38 mitogen-activated protein kinase (MAPK) is implicated in inflammatory mediator production (IL-1beta, iNOS, COX-2).
Purpose of the Study:
- To investigate the effect of the p38 MAPK inhibitor SB203580 on intestinal transit after burn injury.
- To elucidate the underlying mechanisms of p38 MAPK's role in burn-induced gut dysmotility.
Main Methods:
- Burned and sham rats were treated with saline, iNOS inhibitor, COX-2 inhibitor, or SB203580.
- Intestinal transit was measured, and gene/protein expression of inflammatory markers (iNOS, COX-2, IL-1beta) and enzyme activities (p38 MAPK, MPO) were assessed.
Main Results:
- Burn injury significantly delayed intestinal transit and increased p38 MAPK, MPO, iNOS, COX-2, and IL-1beta levels.
- SB203580 treatment almost completely normalized intestinal transit.
- SB203580 inhibited p38 MAPK and MPO activity and reduced inflammatory marker expression.
Conclusions:
- Burn-induced delayed intestinal transit is linked to the p38 MAPK pathway.
- Inhibiting p38 MAPK ameliorates gut dysmotility by reducing iNOS, COX-2, and IL-1beta.
- p38 MAPK is a potential therapeutic target for managing gut dysfunction post-burn injury.
