title: Protective role of metalloproteinase inhibitor (AE-941) on ulcerative colitis in rats.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Gastroenterology, First Afﬁliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors: Jing-Wei
authors: JW
authors: Mao
authors: Xiao-Mei
authors: XM
authors: He
authors: Hai-Ying
authors: HY
authors: Tang
authors: Ying-De
authors: YD
authors: Wang
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000517:prevention & control; D003106:Colon / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014020:Tissue Extracts; C111481:shark cartilage extract; D045726:Metalloproteases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: AE-941; Extracellular matrix; Matrix metalloproteinase-2; Matrix metalloproteinase-9; Ulcerative colitis