The Expression Of MAdCAM-1 And The Therapeutic Efficacy Of NO Donor In Oxazolone-Induced Colitis

Objective To investigate the expression of MAdCAM-1 and the therapeutic efficacy of long-acting NO donor DETA NONOate and rapid releasing NO donor GTN in oxazolone-induced colitis of C57BL/6 mice.Methods 32 C57BL/6 male mice were randomly divided into 4 groups: 1)control group;2)oxazolone-induced colitis group;3)GTN group;4) DETA NONOate group.The experimental colitis model were established by presensitizing and coloclysising with solution of oxazolone-ethanol. Mice of each group were sacrificed after treated with corresponding agents. The disease activity index,macroscopic score and histological score in each group were evaluated;The expression of MAdCAM-1 and NF-κB were determined by immunohistochemical staining;The plasma Nitric oxide levels were determined using a nitrate reductase reaction;The MPO activity in colonic tissue was analyzed.Results 1 The DAI of oxazolone-induced colitis group and GTN group increased since oxazolone injection rectally,but the DAI of DETA NONOate group did not changed obviously. 2 In oxazolone-induced colitis group,the macroscopic score (3.13±0.84) were significantly higher than those of control group (0.38±0.52, p＜0.01) and DETA NONOate group (1.38±0.52, p＜0.01),but similar to GTN group (2.88±0.84, P＞0.05).3 In oxazolone-induced colitis group,the histological score (20.31±2.63) were significantly higher than those of control group (0.88±0.83, p＜0.01) and DETA NONOate group (11.13±1.48, p＜0.01),but similar to GTN group (18.81±2.48, P＞0.05).4 In oxazolone-induced colitis group,the expression of NF-κB (IOD: 30.29±8.68) in colon mucosa was significantly higher than that of control group (7.38±2.29, P＜0.01) and DETA NONOate group (12.60±3.54, P＜0.01),but similar to GTN group (26.81±8.56, P＞0.05).5 In oxazolone-induced colitis group,the expression of MAdCAM-1 (IOD: 17.60±6.53) in colon mucosa was significantly higher than that of control group (4.08±1.30, P＜0.01) and DETA NONOate group (8.42±2.16, P＜0.01),but similar to GTN group (14.37±5.85, P＞0.05).6 In oxazolone-induced colitis group,the level of plasma Nitric oxide (54.51±22.28) was significantly higher than that of control group (32.17±14.88, P＜0.05), but significantly lower than those of DETA NONOate group (88.53±24.77, P＜0.05) and GTN group (80.12±19.79, P＜0.05).7 In oxazolone-induced colitis group,the MPO activity in colonic tissues (3.83±0.60) was significantly higher than those of control group (1.75±0.25, P＜0.01) and DETA NONOate group (2.76±0.48, P＜0.01), but similar to GTN group (3.55±0.59, P＞0.05). 8 There were significant positive correlations between the expression of MAdCAM-1 and the histological score (r=0.786, P＜0.05),the MPO activity (r=0.833, P＜0.05) and IOD of NF-κB (r=0.833, P＜0.05).Conclusions The expression of MAdCAM-1 increased significantly in colonic tissue of oxazolone-induced mice colitis. The inflammatory parameters decreased tremendously after treatment with DETA NONOate but not GTN.According to these results, DETA NONOate may be served as a valuable biological agent for UC treatment.