[Changes in tight junction protein expression and permeability of colon mucosa in rats with dextran sulfate sodium-induced inflammatory bowel disease]

Yan-Xia Rao, Jie Chen, Lei-Lei Chen, Wei-Zhong Gu, Xiao-Li Shu
Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics 2012, 14 (12): 976-81

OBJECTIVE: To develop an experimental rat model of inflammatory bowel disease (IBD) by administration of dextran sulfate sodium (DSS), and to observe changes in the tight junction protein expression and permeability of colon mucosa.

METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control (n=27) and IBD model groups (n=27). In the IBD model group, IBD was induced by 6-day administration of 3% DSS in water followed by 14-day administration of water only. The control group was fed with water only. Pathological changes in colon mucosae were observed on days 7, 14 and 21 after DSS administration. Colon tissue specimens were collected on day 21 for measuring myeloperoxidase (MPO) activity. The transepithelial electric resistance (TEER), transepithelial potential difference (TEPD) and short circuit current (Isc) of the specimens were measured by Ussing chamber. Real-time PCR and Western blot were used to measure the mRNA and protein expression of tight junction proteins in colon epithelia.

RESULTS: In the IBD model group, diarrhea, hemafecia and weight loss were seen. Inflammation occurred mainly in the distal colon and was characterized by crypt abscess and inflammatory cell infiltration. The IBD model group showed significantly increased MPO activity (P<0.01), significantly decreased TEER (P<0.01) and TEPD (P<0.01), and significantly increased Isc (P<0.01) compared with the control group. No claudin 2 expression of mRNA and protein was detected in the control group, and they were expressed in the IBD model group. The expression levels of claudin 3, occludin and ZO-1 in the IBD model group were significantly decreased compared with in the control group (P<0.01).

CONCLUSIONS: IBD rats show colonic barrier dysfunction and changes in the expression of tight junction proteins. The changes in the expression of tight junction proteins may contribute to colonic barrier dysfunction in cases of IBD in the chronic recovery stage.

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