摘要
目的 探讨溃疡性结肠炎患者肠粘膜κ基因结合核因子 (NF κB)的活化以及柳氮磺胺吡啶 (SASP)和糖皮质激素对其的影响。方法 31例溃疡性结肠炎患者中 17例使用过药物 (SASP或SASP +糖皮质激素 )治疗 ,14例未用过任何与溃疡性结肠炎治疗相关的药物 ,11例同期结肠癌患者(取其癌旁正常组织 )作为对照。采用凝胶电泳迁移率改变分析 (EMSA)检测NF κBDNA结合活性 ;Western蛋白印迹分析检测NF κBp6 5蛋白表达情况 ;免疫组化方法原位检测肠粘膜组织中NF κBp6 5蛋白的表达情况 ;荧光双标激光共聚焦显微镜确定表达NF κBp6 5的细胞类型。结果 溃疡性结肠炎患者肠粘膜NF κBp6 5的表达和NF κBDNA结合活性与对照组比较明显升高 (P <0 .0 5 ) ,且与炎症程度有关 ;溃疡性结肠炎患者肠粘膜巨噬细胞、T淋巴细胞、B淋巴细胞以及隐窝上皮细胞均有NF κBp6 5的活化 ;糖皮质激素和SASP明显抑制NF κB的活性及表达。结论 NF κB活性和表达的增加可能与溃疡性结肠炎的发生发展有关 ;糖皮质激素和SASP的抗炎作用可能是通过抑制NF κB的活性实现的。NF κB可能为溃疡性结肠炎新药的研究与开发提供一个有价值的靶标。
Objective To investigate the activation and expression of nuclear factor κB (NF κB) and effects of anti inflammatory treatment on NF κB in the intestinal mucosa of patients with ulcerative colitis (UC). Methods Ten pieces of colon mucosal biopsy specimens were obtained from 31 cases with UC, 17 of which received sulphasalazine (SASP)or SASP plus glucocorticoid and 14 of which received no medication. Samples of normal mucosa around the lesion taken from 11 patients with colon cancer were used as controls. NF κB DNA binding activaty was evaluated by electrophoretic mobility shift assay. NF κB p65 expression was determined by Western blot analysis and immunohistochemical staining with a NF κB p65 antibody. The type of cells containing activited NF κBp65 was identified by double immunofluorescence confocal laser scanning microscopy. Results The expression of NF κB p65 and NF κB DNA binding activity were significantly higher in patients with UC than in the control ( P <0.05), and were correlated with the degree of inflammation. The NF κB expression was significantly stronger in the nuclei than in the cytoplasm in patients with UC without pharmacotherapy. The NF κB espression in nuclei was significantly stronger in the group without pharmacotherapy than in the group with pharmacotherapy ( P <0.05). Only a few NF κB p65 positive cells were seen in the controls. NF κBp65 expression was found in all major subsets of mononucler cells, including macrophages, B lymphocytes, T lymphocytes, and cryptal epithelial cells. Conclusion The increased activation of NF κB and increased expression of NF κB may be involved in the pathogenesis of UC. Glucocorticoids and SASP strongly inhibited NF κB activation and expression. The inhibition of NF κB activation may be a central part of the anti inflammatory action of glucocorticoids and SASP, which might represent an important pharmacological mechanism in treatment of patients with UC. NF κB will be an important target for cytokine based therapy of UC.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2002年第6期384-388,共5页
National Medical Journal of China
基金
国家自然科学基金资助项目 ( 30 1 70 4 2 6)
教育部高等学校博士学科点专项科研基金资助项目 ( 2 0 0 0 5 4 )
四川省卫生厅科研基金资助项目 ( 2 0 0 0 0 1 )
