Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats.

AIM: To investigate the modulatory effect of recombinant-expressed vasoactive intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

METHODS: 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 (rVIPa1nmol , rVIPa2nmol , rVIPa4nmol ). 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.

RESULTS: Administration with 2 nmol rVIPa prevented TNBS-induced necrosis, hyperemia, swelling, inflammation, etc ., pathologic changes observed in the inner surface of colon in experimental rats. Moreover, rVIPa significantly decreased colonic TNF-α level ( P < 0.001), MPO activity ( P < 0.001) and serum endotoxin level ( P < 0.01), and remarkably increased colonic IL-10 content ( P < 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 ( P < 0.05) and ZO-1 ( P < 0.05), NF-κB p65 ( P < 0.01) and IκBα ( P < 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.