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Updated: Jun 21, 2026

A TNBS-Induced Rodent Model to Study the Pathogenic Role of Mechanical Stress in Crohn's Disease
Published on: March 1, 2022
[Changes of mast cells and gut hormones in rats with TNBS-induced ulcerative colitis]
Ping Zhao1, Lei Dong, Jin-Yan Luo
1Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710004, China. peggyzhao@163.com
Objective:
To investigate the role of mast cells and gut hormones and their interactions in TNBS-induced ulcerative colitis.
Methods:
Rat models of ulcerative colitis were established by a single intracolonic injection of 100 mg/kg TNBS (in 0.3 ml 50% ethanol). At 0, 6, 11, 16, 21 days after TNBS injection, the rats were sacrificed to determine the count of the mast cells. Histamine level in the whole blood, and the levels of histamine, substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SS) in the distal colons were measured by fluorimetry or radioimmune assay. Immunofluorescence double staining was used to observe the relationship of the mast cells with SP, VIP, and SS positive nerve fibers.
Results:
On day 6 after TNBS injection, obvious ulcers occurred in the distal colon of the rats with significantly increased histamine level in the whole blood (P<0.05) but significantly decreased colonic histamine levels (P<0.05). The histamine levels in the whole blood and distal colon gradually recovered the normal levels. The mast cells significantly increased on day 16 (P<0.05) and maintained the high level till day 21. The distribution of mast cells was altered after TNBS injection, and the cells were found to aggregate in the myenteric region. SP levels in the distal colon significantly increased on day 11 (P<0.05) and maintained the high level till day 21. Immunofluorescence double staining revealed numerous mast cells close to the SP- and VIP-positive nerve fibers at different time points after TNBS injection. VIP positivity and the number of VIP-positive nerve fibers in the myenteric region were markedly increased, but no mast cells were observed in association with SP- and VIP-positive nerve fibers. The distribution of MC was not found to associate with the SS-positive nerve fibers.
Conclusion:
The mast cells and histamine released by them, as well as parasecretion of SP and VIP, participate in tissue damage by TNBS-induced colitis. Bidirectional neuroimmunomodulation of the mast cells, SP and VIP have important effect on the development of TNBS-induced colitis.
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