抗炎药物对溃疡性结肠炎患者肠黏膜组织NF-κB的活化和细胞黏附分子表达的影响

The Effects of Anti-inflammatory on Activation of Nuclear Factor-κB and Expression of Cell Adhesion Molecules in Patients with Ulcerative Colitis

探讨抗炎药物柳氮磺胺吡啶 (SASP)和糖皮质激素对溃疡性结肠炎 (Ulcerative colitis,UC)患者肠黏膜活检组织细胞间黏附分子 (Intercellular adhesion molecule- 1,ICAM- 1)与血管细胞黏附分子 (Vascular cell adhes-ion molecule- 1,VCAM- 1) m RNA和蛋白表达的影响 ,以及黏附分子 m RNA的表达与 NF- κB活化的关系。2 7例来自四川大学华西医院的 U C患者 (符合 1993年太原会议溃疡性结肠炎诊断标准 )被纳入本研究。其中 15例使用过药物 (SASP或 SASP+糖皮质激素 )治疗 ,12例未用过任何与 U C治疗相关的药物 ,9例同期结肠癌患者 (取其癌旁正常组织 )被作为对照。采用逆转录聚合酶链反应 (RT- PCR)检测 ICAM- 1与 VCAM- 1m RNA的表达 ;酶联免疫吸附试验 (EL ISA)测定 ICAM- 1与 VCAM- 1蛋白水平。凝胶电泳迁移率改变分析 (EMSA)检测 NF-κB DNA结合活性。结果显示 :与对照组相比 ,UC患者肠黏膜活检组织 ICAM- 1与 VCAM- 1m RNA和蛋白表达以及 NF-κBDNA结合活性明显升高 (P<0 .0 5 ) ;糖皮质激素和 SASP明显抑制 U C患者 NF-κB DNA结合活性 ,降低 ICAM- 1与 VCAM- 1m RNA和蛋白的表达 (P<0 .0 5 ) ;ICAM- 1和 VCAM- 1基因激活与 NF-κB DNA结合活性呈显著正相关 (ICAM- 1:r=0 .86 5 2 ,P<0 .0 5 ;VCAM-

The purpose of this study is to assess the effects of anti-inflammatory on activation of nuclear factor-κB and mRNA and protein expression of intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative colitis(UC). A total of 27 cases with UC were investigated. 15 cases received sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did not receive any medication related with UC. Normal mucosa from 9 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were determined by reversal transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent assay (ELISA). NF-κB DNA binding activity was evaluated by electrophoretic mobility shift assay(EMSA). The results showed that NF-κB DNA binding activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased significantly in patients with UC, compared with normal control (P<0.05). Glucocorticoids and SASP markedly inhibited NF-κB activation and significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1(P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant positive correlation with the NF-κB DNA binding activity(r=0.8652 P<0.05, r=0.7902, P<0.05, respectively). We concluded that NF-κB is a major and essential factor in regulating the expression of adhesion molecules, it plays an important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC via inhibition of NF-κB activation and reduction of adhesion molecules expression.