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小剂量环孢素A治疗溃疡性结肠炎对肠黏膜中NFAT活性及GM-CSF表达的影响

Low-dose cyclosporine A in the treatment of ulcerative colitis and its effect on NFAT activity and GM-CSF expression in colonic mucosa
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摘要 目的:研究小剂量环孢素A(CsA)治疗的溃疡性结肠炎(UC)患者肠黏膜中核转录因子(NFAT)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的变化,及其对黏膜炎症的影响.方法:UC患者14例经CsA治疗,采用凝胶电泳迁移率改变分析法(EMSA)检测肠黏膜NFAT治疗前后活性的变化,半定量RT-PCR法检测肠黏膜中GM-CSFmRNA的改变,治疗前后对肠黏膜炎症程度进行评估.结果:UC患者治疗后肠黏膜NFAT活性下降(0.80±0.31vs0.50±0.20,P<0.05),GM-CSFmRNA表达也有降低(1.09±0.07vs0.49±0.03,P<0.01),肠黏膜炎症程度也下降(P<0.05).结论:小剂量CsA治疗UC有效,其机制与调控NFAT的转录活性有关,并进一步降低激活因子GM-CSF的表达. AIM: To evaluate the effect of low-dose cyclosporine A on the expressions of nuclear factor of activated T cell (NFAT) and granulocyte macrophage colony stimulating factor ( GM-CSF), and on the inflammation degree of colonic mucosa in patients with ulcerative colitis (UC). METHODS: Fourteen UC patients were treated with cycylosporine A. DNA-binding activity of NFAT in colonic nuclear extracts was detected by gel electrophoretic mobility shift assay (EMSA). The expression of GM-CSF mRNA was identified by semi-quantitative RT-PCR. The degree of inflammation was also evaluated pathologically before and after therapy. RESULTS: The NFAT activity was decreased after the treatment of cycylosporine A (0.80 ±0.31 vs 0.50 ±0.20, P〈0.05) and GM-CSF mRNA level was signitlcanfly decreased as well ( 1.09 ±0.07 vs0.49 ± 0.03, P 〈 0.01 ). The degree of inflammation was decreased evidently after the treatment ( P 〈 0.05 ). CONCLUSION: Low-dose cyclosporine A is effective in the treatment of refractory UC, and the mechanism may be correlated with NFAT inactivation and inhibition of GM-CSF gene expression.
出处 《第四军医大学学报》 北大核心 2007年第11期1042-1044,共3页 Journal of the Fourth Military Medical University
基金 全军"十一五"课题(06MA089)
关键词 结肠炎 溃疡性 环孢素A 核转录因子 粒细胞巨噬细胞集落刺激因子 colitis, ulcerative cyclospofine A nuclear factor granulocyte macrophage colony stimulating factor
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