World journal of gastroenterology 24(6) 706-715 doi 10.3748/wjg.v24.i6.706
To investigate the modulatory effect of recombinant-expressed vasoactive intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.
Forty-eight rats were randomized into six groups: normal control group (Control), model control group (TNBS), ethanol treatment group (ETOH), and VIP treatment groups with different dosage (rVIPa, rVIPa, rVIPa). Diarrhea and bloody stool were observed. Colonic damage was evaluated histologically. The levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), myeloperoxidase (MPO) and endotoxin in colonic tissue and serum were determined by enzyme-linked immunosorbent assay (ELISA). The expression of occludin, ZO-1, Toll-like receptor 4 (TLR4), and nuclear factor-kappa B p65 (NF-κB p65), IκBα, and p-IκBα were detected by Western blot.
Administration with 2 nmol rVIPa prevented TNBS-induced necrosis, hyperemia, swelling, inflammation,., pathologic changes observed in the inner surface of colon in experimental rats. Moreover, rVIPa significantly decreased colonic TNF-α level (< 0.001), MPO activity (< 0.001) and serum endotoxin level (< 0.01), and remarkably increased colonic IL-10 content (< 0.001) in rats with TNBS-induced colitis. Furthermore, compared to the TNBS-induced colitis group, 2 nmol rVIPa treatment up-regulated the levels of occludin (< 0.05) and ZO-1 (< 0.05), NF-κB p65 (< 0.01) and IκBα (< 0.001), and down-regulated the levels of TLR4. CONCLUSION
rVIPa ameliorates TNBS-induced colonic injury and inflammation and effectively protected the intestinal mucosal barrier function in rats. The mechanism may be related to TLR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders.