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Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation
Published on: September 11, 2012
Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility
Nicolas T Schwarz1, Jörg C Kalff, Andreas Türler
1Chirurgische Universitätsklinik der Friedrich-Wilhelms-Universität, Bonn, Germany.
Background And Aims:
Small bowel manipulation initiates an intense molecular and cellular inflammatory response within the jejunal muscularis, which causes ileus. The current objective was to investigate pan-enteric inflammatory molecular and functional motility alterations of the muscularis from the unmanipulated stomach and colon initiated by selective jejunal manipulation.
Methods:
Rat jejunum was manipulated, and animals sacrificed between 0-24 hours. In vivo gastric emptying, gastrointestinal transit, and in vitro colonic circular muscle recordings were measured. Reverse-transcriptase polymerase chain reaction (RT-PCR) and electromobility shift assay (EMSA) of gastric, jejunal, and colonic muscularis extracts were performed. Whole mounts were histochemically stained for myeloperoxidase leukocytes.
Results:
Surgical manipulation suppressed jejunal contractions that were significantly prevented by dexamethasone pretreatment. Selective jejunal manipulation also suppressed in vivo gastric emptying, gastrointestinal transit, and in vitro colonic circular muscle contractility. Nuclear factor interleukin-6 (NF-IL-6) was activated within the gastric and colonic muscularis. RT-PCR showed a 14.9-, 8.1-, and 11.4-fold up-regulation of IL-6 messenger RNA within the jejunal, gastric, and colonic muscularis, respectively. EMSA showed a 30.6-, 14.2-, and 20.8-fold increased activation of signal transducer and activator of transcription (STAT) proteins in jejunal, gastric, and colonic muscularis extracts, respectively. Tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase showed a significant up-regulation in the manipulated jejunum, as well as the unmanipulated gastric and colonic muscularis. Neutrophils were significantly recruited into all gastrointestinal regions.
Conclusion:
Selective small bowel manipulation leads to a molecular, cellular, and functional pan-enteric "field effect" phenomenon in the unmanipulated gastric and colonic muscularis.
Insights
Selective small bowel manipulation triggers widespread inflammation and motility issues throughout the entire gastrointestinal tract. This "field effect" impacts the stomach and colon, not just the manipulated jejunum.
Area of Science:
- Gastroenterology
- Inflammation Research
- Surgical Physiology
Background:
- Small bowel manipulation causes inflammation and ileus in the jejunal muscularis.
- The study aimed to understand if jejunal manipulation affects unmanipulated stomach and colon.
Purpose of the Study:
- To investigate pan-enteric inflammatory and motility changes in the muscularis of the stomach and colon due to selective jejunal manipulation.
- To assess the molecular and functional consequences across the entire gastrointestinal tract.
Main Methods:
- Rat jejunum was manipulated, with data collected 0-24 hours post-manipulation.
- Measured in vivo gastric emptying, GI transit, and in vitro colonic muscle contractility.
- Utilized RT-PCR, EMSA, and histochemical staining for molecular and cellular analysis.
Main Results:
- Jejunal manipulation suppressed contractions, gastric emptying, and colonic motility, effects mitigated by dexamethasone.
- Significant upregulation of IL-6 mRNA and STAT protein activation observed in jejunal, gastric, and colonic muscularis.
- Increased expression of TNF-alpha, COX-2, and iNOS, with neutrophil recruitment across all GI regions.
Conclusions:
- Selective small bowel manipulation induces a pan-enteric "field effect" phenomenon.
- This effect involves molecular, cellular, and functional alterations in unmanipulated gastric and colonic muscularis.
- Highlights the interconnectedness of the gastrointestinal tract in response to localized injury.
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