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葡聚糖硫酸钠诱导结肠炎小鼠NF-κB活性及其对ICAM-1表达的调控
Activation of nuclear factor-κB and its modulalorg effects on intercellular adhesion molecule-1 expression in mice with dextran sulphate sodium-induced rat colitis
【摘要】 目的探讨葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠NF-κB活性、ICAM-1蛋白表达变化及NF-κB对其调控作用。方法取健康雄性BABC/L小鼠20只,采用5%DSS溶液结肠炎小鼠模型和0.9%盐水溶液(NS)为正常对照组。免疫组化方法检测细胞间粘附分子(ICAM-1)和NF-κBp65表达水平,凝胶滞留迁移试验(EMSA)测定NF-κB的DNA结合活性。结果DSS组较NS组NF-κBDNA结合活性显著升高,具统计学意义(P<0.01),NF-κBp65成份主要表达于粘膜下层的炎症细胞及部分血管内皮细胞,出现核移位现象,正常对照组仅少数细胞表达p65,ICAM-1。相关性分析提示NF-κB活性与ICAM-1表达呈正相关性。结论DSS诱导结肠炎小鼠结肠粘膜的NF-κB明显活化,可能上调了ICAM-1基因的表达,参与肠道炎症的发生发展。
【Abstract】 Objective To investigate the changes in the activity of nuclear factor-κB (NF-κB) in mice with dextran sulphate sodium (DSS)-induced rat colitis and its modulalorg effect on intercellular adhesion molecule-1 (ICAM-1) expression. Methods Twenty normal male mice were randomized into DSS group and normal saline (NS) control group according to a matched-pair design. From days 1 to 7,the mice in DSS group were subjected to oral administration of 5%DSS solution,and from days 8 to 20,NS was given instead,for a total of 3 cycles. In the control group,only NS was administered. The colonic pathology was observed using HE staining and the mucosa 1 damage was scored for each mouse. The DNA-binding activity of NF-κB was tested by electrophoretic mobility shift assay,and the expressions of ICAM-1 and NF-κB p65 were detected using immunohistochemistry. Results The DNA-binding activity of NF-κB was significantly increased in DSS group as compared with NS group. ICAM-1 and p65 expressions were detected in the nuclei of the vascular endothelial and inflammatory cells,especially in the mucosa and submucosa,but such positive cells were seldom observed in NS group. A positive correlation was found between the DNA-binding activity of NF-κB and ICAM-1 expression. Conclusion NF-κB activation is an important event in the development of DSS-induced colitis in that activated NF-κB upregulates ICAM-1 expression during colonic inflammation.
【Key words】 dextran sulphate sodium; colitis; nuclear factor-κB; intercellular adhesion molecule-1;
- 【文献出处】 南方医科大学学报 ,Journal of Southern Medical University , 编辑部邮箱 ,2008年04期
- 【分类号】R574.62
- 【被引频次】8
- 【下载频次】173