儿童溃疡性结肠炎黏膜肿瘤坏死因子-α及核因子-κB的表达

Expression of tumor necrosis factor-αand nuclear factor-κB in chilhood ulcerative colitis

目的 了解肿瘤坏死因子 (TNF) α及核因子 (NF) κB在儿童溃疡性结肠炎 (UC)发病中的作用 ,原位研究了儿童UC肠粘膜中TNF α和NF κB的表达及相互关系。方法 应用抗巨噬细胞表面抗原CD68抗体 ,抗TNF α抗体及抗NF κBp65抗体 ,对 3 9例儿童溃疡性结肠炎活检标本 ( 2 1例为活动期 ,18例为非活动期 )及 7例因消化道息肉出血或腹痛肠镜正常的结肠粘膜对照标本进行免疫组织化学染色。结果 活动性UC结肠粘膜中每高倍镜视野下 ,CD68、TNF α及NF κBp65阳性细胞中位数 (四分位间距 )分别为 44 0 ( 3 1 5～ 48 2 )、42 7( 19 5～ 65 0 )及 50 7( 3 0 0～ 58 0 ) ;非活动性UC粘膜中CD68、TNF α及NF κBp65阳性细胞中位数 (四分位间距 )分别为 9 2 ( 7 9～ 16 6)、5 5( 2 5～ 9 1)及4 2 ( 3 0～ 8 4) ;对照组分别为 5 3 ( 4 3～ 8 7)、3 0 ( 0 0～ 6 3 )及 3 3 ( 0 0～ 4 0 )。活动性UC组CD68、TNF α及NF κBp65阳性细胞数显著高于非活动性UC组及对照组 (P均 <0 0 0 1) ;非活动期UC组CD68阳性细胞数显著高于对照组 (P =0 0 0 8) ;同时作回归分析 ,UC结肠粘膜中TNF α阳性细胞数与NF κB活化阳性细胞数存在明显正相关 (r =0 885,P <0 0 0 1)。结论 巨噬细胞、TNF α及NF κB在儿童活动性UC?

Objective It has been proposed that aberrant immunity of local bowel mucosa may cause ulcerative colitis (UC) and the tumor necrosis factor-α (TNF-α) and nuclear factor -κB ( NF-κB ) may play a role in the development of this disease. To investigate the role of TNF-α and NF-κB in childhood UC, the expression of TNF-α and NF-κB in the bowel mucosa and their relationship were studied. Methods Using anti-CD68, anti-TNF-α and anti-NF-κBp65 antibodies, the cytokine immunoreactivities in the bowel mucosa of 39 cases of childhood UC (active UC: n=21, non-active UC: n=18) were detected by immunohistochemistry. The control specimens of normal bowel mucosa were collected from 7 cases with colorectal polyp or abdominal pain by sigmoidoscopy.Results The numbers (median: interquartile range) of CD68 + cells, TNF-α + cells and NF-κBp65 + cells were 44.0(31.5-48.2), 42.7(19.5-65.0) and 50.7(30.0-58.0) in the active UC mucosa, and were 9.2(7.9-16.6), 5.5(2.5-9.1) and 4.2 (3.0-8.4) in non-active UC muc osa, and 5.3(4.3-8.7), 3.0(0.0-6.3) and 3.3(0.0-4.0) in the control mucosa, respectively. The levels of CD68, TNF-α and NF-κBp65 expressions in the active UC were significantly higher than those in the non-active UC(P<0.001) and the controls (P <0.001). The expression level of CD68 in non-active UC was much higher than that in the controls (P =0.008). Using the correlation analysis, a positive correlation between TNF-α and NF-κB activation was found (r=0.885, P <0.001).Conclusions Macrophages TNF-α and NF-κB may play an important role in the pathophysiologic mechanism of childhood active UC. The activation of NF-κB may be associated with the release of TNF-α.