溃疡性结肠炎和克罗恩病患者端粒结合蛋白TRF1和TRF2及RAP1 mRNA表达的变化

Altered mRNA Expression of Telomere Binding Proteins(TRF1,TRF2 and RAP1) in Ulcerative Colitis and Crohn′s Disease

目的观察溃疡性结肠炎和克罗恩病患者端粒结合蛋白TRF1、TRF2、RAP1 mRNA的表达,并分析其与疾病的关系。方法选取34例炎性肠炎患者(溃疡性结肠炎18例,克罗恩病16例)和14例健康志愿者(正常对照组)为研究对象,抽取肘静脉血20 m l,分离外周血单核细胞,并经植物血细胞凝集素激活后纯化为激活T淋巴细胞(CD2+5T淋巴细胞)。用RT-PCR法测定受试者外周血单核细胞和激活T淋巴细胞TRF1、TRF2、RAP1 mRNA的表达。结果溃疡性结肠炎组和克罗恩病组患者外周血单核细胞TRF1 mRNA表达水平及激活T淋巴细胞TRF2 mRNA表达水平均较正常对照组显著降低,差异有统计学意义(P<0.05);溃疡性结肠炎组患者激活T淋巴细胞RAP1 mRNA表达水平显著低于正常对照组,差异亦有统计学意义(P<0.01),但是克罗恩病组患者激活T淋巴细胞RAP1 mRNA表达水平与正常对照组比较差异无统计学意义(P>0.05);另外,溃疡性结肠炎患者外周血单核细胞TRF1 mRNA表达水平较克罗恩病组显著增加,差异有统计学意义(P<0.01)。结论感染性肠炎患者外周血T淋巴细胞TRF2和RAP1mRNA表达下调,表明端粒结合蛋白在端粒调节中起到一定作用,炎性肠病促进了患者端粒融合和染色体异常。此结果也表明端粒脱帽的系统性进程可能作为癌症风险相关的炎性肠病的生物标志。

Objective To observe mRNA expression in telomere binding proteins （TRF1, TRF2 and RAPI ） in ulcerative colitis （UC） and Crohn＇s disease （CD） and analyze the relationship. Methods Peripheral blood mononuclear cells （PBMC） obtained from 34 IBD patients （ 18 ulcerative colitis and Crohn＇s disease） and 14 controls were activated by phytohaemagglutinin and purified to yield activated （ CD25 ） T lymphoeytes. TRF1, TRF2 and RAP1 mRNA expression in PBMC and activated T lymphocytes was measured by RT- PCR. Results TRF1 mRNA levels in PBMC and TRF2 mRNA levels in T lymphocytes were significantly reduced in both UC and CD subjects compared with the control group （P 〈 0. 05）. Levels of RAP1 mRNA in T lymphocytes were significantly lower in UC subjects compared with the control group （P 〈0. 01 ） , but not in CD subjects （P 〉 0. 05）. Levels of TRF1 mRNA in PBMC of UC subjects were significantly increased compared with CD subjects （P 〈 0. 01 ）. Conclusion The down regulation of TRF2 and RAP1 mRNA expression in CD25 T - lymphoeytes in IBD suggests that these telomere binding proteins play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in UC. These findings may also indicate a systemic process of telomere uncapping which could represent a biomarker for IBD associated cancer risk.