系统性红斑狼疮患者Ets-1表达及其调控微小RNAs的研究  

Expression of Ets-1 and its related microRNAs in patients with systemic lupus erythematosus

作　　者：马倩[1] 李向培[1] 陶金辉[1] 厉小梅[1] 汪国生[1] 钱龙[1] 项楠[1] 任启洁[1] 何孝亮[1] 方璇[1] 

机构地区：[1]安徽医科大学附属省立医院风湿免疫科,合肥230001

出　　处：《中华风湿病学杂志》2013年第12期800-804,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（81373186）

摘　　要：目的检测系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMCs）中Ets-1及其相关微小RNAs（miRNAs）的表达水平，探讨其在SLE发病中的作用。方法以Ets-1为靶基因，利用生物信息学方法（miRanda、TargetScan和PicTar软件）筛选出相关miRNAs（miR．326、miR．155、miR-21、miR-222o收集SLE患者50例[SLE疾病活动指数（SLEDAI）评分≥5分为活动组30例，〈5分为稳定组20例]，健康志愿者20名作为健康对照组。采用实时荧光定量聚合酶链反应（PCR）检测PBMCs中Ets-1和miRNAs的表达水平，分析其与临床及实验室指标的相关性。结果①SLE活动组和稳定组Ets-1表达水平[0.54（0．37～0．66）和0．50（0．35-0．71）]与健康对照组[0．74（0．64～1．14）]相比均显著减低（Z=-3．525，P〈0．01；Z=-3．273，P〈0．01）。②SLE活动组miR-326、miR-155、miR-221、miR-222表达水平比SLE稳定组、健康对照组显著增高（P〈0．05）。③SLE组miRNAs与Ets-1之间无相关性（P〉0．05）。④SLE组Ets-1与SLEDAI之间无相关性（P〉0．05），4种miRNAs与SLEDAI呈正相关（r=0．475，0．542，0．397，0．507；P〈0．05）。⑤SLE组Ets-1与抗核抗体呈负相关（r=-0．366，P〈0．05），miR-155、miR-221、miR-222与抗核抗体呈正相关（r=0．363，0．371，0．371；P〈0．05）。结论SLE患者外周血PBMCs中Ets-1表达降低，其可能与SLE发病相关；miR-326、miR-155、miR-221、miR-222在SLE活动组表达升高，可能作为SLE疾病活动的生物学标志。Objective To investigate the expression of Ets-1 and its related microRNAs （miRNA） in peripheral blood mononuclear cells （PBMCs） of patients with systemic lupus erythematosus （SLE）, and to explore their effects on the pathogenesis of SLE. Methods miRNA was identified by bioinformatics analysis and the target prediction indicated that Ets-1 was a putative target of miR-326, miR-155, miR-221 and miR-222. PBMCs were separated from the peripheral blood in 50 patients with SLE （the SLEDAI of 30 SLE patients was higher than 5 and were included as the active group, while SLEDAI less than 5 were included as disease remission group） and 20 healthy individuals （the control）. The levels of Ets-1 and the miRNAs were determined by quantitative reverse transcription PCR （qRT-PCR）,the correlation of them with the clinic and laboratory parameters of SLE were analyzed. Results ① Compared to the control group [0.74（0.64-1.14）], the expression of PBMCs Ets-1 was significantly lower in the active and remission group [0.54（0.37-0.66） and 0.50（0.35-0.71）] （Z=-3.525, P〈0.01 ; Z=-3.273, P〈0.01）. ② Compared to the remission group and the control group, the expression of miR-326, miR-155, miR-221, miR-222 in PBMCs were higher in the active group（P〈0.05）. ③ The expression of Ets-1 was not correlated with miRNAs in SLE patients （P〉0.05）. ④ The SLEDAI score of SLE patients was not correlated with the expression level of Ets-1 （P〉0.05）, there was significant positive correlation between the expression level of miRNAs （r=0.475, 0.542, 0.397, 0.507; P〈0.05） and SLEDAI score. ⑤ The titer of ANA of SLE patients was significantly negatively correlated with the expression level of Ets-1 （r=-0.366, P〈0.05）, and there was significantly positive correlation between the expression level of miR-155, miR-221, miR-222 and the titer of ANA （r=0.363, 0.371, 0.371; P〈0.05）. Conclusion The expression of PBMCs Ets-1 is significantly lower in the SLE group, and Ets-1 may b

关 键 词：红斑狼疮 系统性 ETS-1 微小RNAS 

分 类 号：R593.241[医药卫生—内科学]