Dynamic progress of 2,4,6-trinitrobenzene sulfonic acid induced chronic colitis and fibrosis in rat model.
OBJECTIVE
To investigate the dynamic progress of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis and fibrosis in rat model.


METHODS
In all, 44 Sprague-Dawley rats were randomly divided into the model and control groups. Colitis was induced by intrarectal injection of 10-30 mg TNBS in 50% ethanol enema weekly for 5 cycles. The control group received an equal volume of 50% ethanol. If the rat died during the procedure, necropsy was performed immediately. At the end of the 2nd, 3rd, 4th and 5th week the rats were sacrificed, and histological damage and fibrosis of the colon were examined using HE and Masson trichrome stain. The concentrations of Th1, Th2, Th17 cytokines in colon tissue were detected by ELISA, intestinal fibrosis-relevant cytokine expressions were detected by fluorescent quantification-polymerase chain reaction.


RESULTS
Colitis model was successfully induced with a low mortality rate. The microscopic colonic damage score, collagen area, Th1/Th17 cytokines and expressions of intestinal fibrosis-relevant cytokines were significantly higher in the model group than those in the control group. Furthermore, the collagen area, content of interleukin 17 and expressions of intestinal fibrosis-related cytokines in the model group were more elevated in the chronic phase (after 3 to 4 cycles) than in the acute phase (P < 0.05).


CONCLUSIONS
Multiple inflammatory responses participate in the formation and dynamic progression of TNBS-induced chronic colitis. In particular, acute colitis may turn into chronic colitis after 3 cycles of TNBS administration. This coincides with the formation of intestinal fibrosis which is concomitantly exacerbated after cycle 4.
Department of Gastroenterology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Mei Ying
MY
Zhu
Yun Min
YM
Lu
Yang Xiao
YX
Ou
Hui Zhen
HZ
Zhang
Wei Xiong
WX
Chen
D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology*; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C526316:CCN2 protein, rat; D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D018793:Interleukin-13; D020381:Interleukin-17; D007376:Interleukin-2; D012333:RNA, Messenger; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor; D015847:Interleukin-4; D014302:Trinitrobenzenesulfonic Acid