端粒重复序列结合蛋白1与2在原发性痛风性关节炎患者中的变化及其临床意义

Expression of telomeric repeat binding protein 1 and telomeric repeat binding protein 2 mRNA and protein in the peripheral blood mononuclear cells of patients with primary gouty arthritis

目的 探讨端粒重复序列结合蛋白（TRF）1和TRF2在原发性痛风性关节炎（GA）发病中可能的作用.方法 将研究对象分为急性期GA（AGA）组77例、非急性期（NAGA）组49例及健康对照组79名.实时荧光定量多聚合酶链反应（RT-qPCR）及蛋白质印迹法分别检测TRF1和TRF2在3组PBMCs中转录水平及蛋白水平的表达.采用单因素方差分析,LSD法两两比较和Spearman相关分析行统计学处理.结果 ①TRF1、TRF2转录水平及蛋白水平在AGA组（0.012 6±0.005 3和0.017 6±0.007 8）和NAGA组（0.009 5±0.003 6和0.014 0±0.004 1）均显著高于健康对照组（0.004 2±0.001 2和0.005 8±0.0019,F=10.818,F=8.869,P均＜0.01）.②在AGA组中TRF2转录水平均与淋巴细胞（LY）呈正相关（r=0.289,P＜0.05）,TRF1转录水平与TRF2（r=0.935,P＜0.01）、LY（r=0.256,P＜0.05）、TG （r=0.281,P＜0.05）、极低密度脂蛋白（VLDL-C）（r=0.291,P＜0.05）均呈正相关.结论 端TRF1、TRF2在原发性GA患者的异常表达及与LY呈正相关,提示其可能参与了痛风的发生发展及免疫与炎症调节.

Objective To investigate the expression levels of telomeric protein telomeric repeat binding protein （TRF） 1 and TRF2 mRNA and protein in the peripheral blood mononuclear cells （PBMCs） of patients with primairy Gouty arthritis （GA）,and the relations between these gene expression levels and disease activity were explored.Methods ① One hundred and twenty-six GA and 79 healthy controls （HC） were enrolled into the study.The clinical data of primary gouty arthritis patients and healthy controls were collected.PBMCs were isolated from blood in vitro.② Real-time quantitative polymerase chain reaction （RT-qPCR） was employed to test the expression of TRF1 and TRF2 mRNA in PBMCs from 77 AGA,49 NAGA and 79 HC,and the differences of gene expression in three groups were compared.③ TRF1 and TRF2 protein were measured by using Western blotting in PBMCs from 15 GA,9 NAGA and 12 healthy controls,and other protein expression in three groups were compared.④ Analysis of covariance,LSD method,and Spearman correlations were used for statistical analysis.Results The expression levels of TRF1 and TRF2 mRNA and protein in the PBMCs of AGA （0.012 6±0.005 3 vs 0.017 6±0.007 8） and NAGA （0.009 5±0.003 6 vs 0.014 0±0.004 1） patients was significantly increased compared to healthy individuals （0.004 2±0.001 2 vs 0.005 8± 0.001 9,F=10.818,F=8.869,P〈0.01）.The expression level of TRF2 was correlated with LY （r=0.289,P〈 0.05）.The expression levels of TRF1 was correlated with TRF2 （r=0.935,P〈0.01）,LY （r=0.256,P〈0.05）,TG （r=0.281,P〈0.05）,VLDL-C （r=0.291,P〈0.05）.Conclusion TRF1 and TRF2 play a key role in the inflammatory immune regulation of GA,and they are involved in the pathogenesis of gouty immune and inflammatory responses.Further study is needed to clarify the expression and functions of telomeric proteins.