Protective role of metalloproteinase inhibitor (AE-941) on ulcerative colitis in rats

Aim: To evaluate the protective role of AE-941, a matrix metalloproteinase (MMP) inhibitor, on ulcerative colitis (UC) in rats.

Methods: Sprague Dawley (SD) rats were randomly divided into three groups: a control group, an AE-941 treatment group, and an UC model group. Rats were sacrificed on days 7, 21, or 56 following administration of treatment by enema and the disease activity index (DAI), colonic mucosa damage index (CMDI) and colonic expression of MMP-2 and MMP-9 were assessed.

Results: DAI and CDMI scores in the UC model group increased significantly compared to the control group at all timepoints (P < 0.001), and also increased significantly at the 21- and 56-d timepoints compared to the AE-941-treated group (DAI: 21- and 56-d = 2.09 ± 0.25, 1.52 ± 0.30 vs 1.55 ± 0.28, 0.59 ± 0.19, respectively, P = 0.040 and 0.007, CMDI: 21- and 56-d = 3.03 ± 0.42, 1.60 ± 0.35 vs 2.08 ± 0.46, 0.86 ± 0.37, respectively, P = 0.040 and 0.005). Furthermore, the colonic expression of MMP-2 and MMP-9 in the UC model group increased significantly compared to the control group (P < 0.001), and also increased compared to the AE-941-treated group on the 21- and 56-d timepoints (MMP-2: 21- and 56-d = 0.6048 ± 0.0522, 0.4163 ± 0.0330 vs 0.3983 ± 0.0218, 0.1093 ± 0.0072, respectively, P = 0.010; MMP-9: 21- and 56-d = 0.6873 ± 0.0472, 0.4328 ± 0.0257 vs 0.5179 ± 0.0305, 0.2673 ± 0.0210, respectively, P = 0.010 and 0.040).

Conclusion: Expression of MMP-2 and MMP-9 increased significantly in rats with UC. AE-941 can reduce colonic mucosal damage by downregulating the expression of MMP-2 and MMP-9.