MAdCAM-1及NF-КB在小鼠恶唑酮结肠炎中的表达及一氧化氮供体的干预作用

Expression of MAdCAM-1 and nuclear factor kappa B and the intervention effect of nitric oxide donor in oxazoloneinduced colitis

目的:探讨MAdCAM-1在恶唑酮结肠炎中的表达及一氧化氮供体DETA NONOate和GTN对恶唑酮结肠炎的干预作用.方法:32只C57BL/6小鼠随机分为正常对照组(A)、恶唑酮结肠炎组(B)、GTN干预组(C)和DETA NONOate干预组(D).除正常对照组外,其余3组均建立小鼠恶唑酮结肠炎模型,两个一氧化氮供体干预后处死小鼠.评价DAI、大体评分和组织学评分;免疫组织化学法检测MAdCAM-1及NF-КB;硝酸还原酶法测定血清中NO含量;测定结肠组织MPO活性.结果:B组小鼠DAI评分自灌肠之日起逐渐增高,而D组则变化不明显.B组小鼠大体评分、组织学评分、NF-КB的表达、MAdCAM-1的表达、MPO活性(3.13±0.84,20.31±2.63,30.29±8.68,17.60±6.53,3.83±0.60)均分别高于A组(0.38±0.52,0.88±0.83,7.38±2.29,4.08±1.30,1.75±0.25,P<0.01)和D组(1.38±0.52,11.13±1.48,12.60±3.54,8.42±2.16,2.76±0.48,P<0.01),而C组则与B组相近.B组小鼠血清NO浓度高于A组(54.51±22.28 vs 32.17±14.88,P<0.05),而低于D组和C组(54.51±22.28 vs 88.53±24.77,80.12±19.79,均P<0.05).B组MAdCAM-1的表达与组织学评分、MPO活性、NF-КB P65 L4值呈正相关(r=0.786,r=0.833,r=0.833,P<0.05).结论:小鼠恶唑酮结肠炎中结肠固有层MAdCAM-1的表达增加,DETA NONOate可能是治疗溃疡性结肠炎的有价值药物.

AIM：To investigate the expression of MAdCAM-1 and nuclear factor kappa B（NF-КB） as well as the intervention of nitric oxide（NO） donor DETA NONOate and GTN in oxazolone-induced colitis. METHODS：Thirty two C57BL/6 mice were randomly divided into 4 groups：group A,B,C and D.The oxazolone experimental colitis model was established in group B,C and D.Mice of group C were treated with GTN and group D with DETA NONOate.The disease activity index （DAI）,macroscopic score and histological score in each group were evaluated.The expression of MAdCAM-1 and NF-КB were determined by immunohistochemical staining.The plasma nitric oxide（NO）levels and the MPO activity in colonic tissues were also analyzed. RESULTS：The DAI in group B and C increased since oxazolone was administered rectally,but it did not changed obviously in group D.The macroscopic score,the histological score,the expression of NF-КB,the expression of MAd- CAM-1 and the MPO activity in group B（3.13±0.84,20.31±2.63,30.29±8.68,17.60±6.53,3.83±0.60）,which were significantly higher than those in group A,respectively（0.38±0.52,0.88±0.83, 7.38±2.29,4.08±1.30,1.75±0.25,P〈0.01）and group D（1.38±0.52,11.13±1.48,12.60±3.54,8.42±2.16,2.76±0.48,P〈0.01）,but similar to those of group C.The level of plasma NO in group B was significantly higher than that of group A （54.51±22.28 vs 32.17±14.88,P〈0.05）,but significantly lower than that of group D and C（54.51±22.28 vs 88.53±24.77,80.12±19.79,all P〈0.05）. There were significant positive correlations be- tween the expression of MAdCAM-1 and the histological score,the MPO activity and IA of NF-КB（r=0.786,r=0.833,r=0.833,P〈0.05）. CONCLUSION：The expression of MAdCAM-1 increases significantly in lumina propria of colonic tissues in oxazolone-induced colitis of mice.According to these results,DETA NONO- ate may serve as a valuable biological agent for UC treatment.