摘要
目的探讨妊娠合并系统性红斑狼疮(SLE)患者DNMTs和MBDs的表达与表观遗传学机制研究。方法随机选择31例单胎妊娠合并SLE患者和30例正常单胎妊娠女性人体内分离CD4+T细胞。采用ELISA检测DNA细胞脱氧甲基胞嘧啶。采用RT-PCR量化ITGAL、PRF1、KIR2DL4、CD70、CD40LG、DNMT1、DNMT3A、DNMT3B、MBD2和MBD4的转录水平。结果妊娠合并SLE患者ITGAL[(18.57±21.51)vs.(7.18±9.36),P=0.0046],PRF1[(21.59±24.28)vs.(10.37±11.25),P=0.0117],以及CD70[(1.48±1.63)vs.(0.71±0.26),P=0.0059]的转录水平均明显增高。且CD40LG与ITGAL的转录水平有明显的正相关性(r=0.468,P=0.005),并且,PRF1与CD40LG之间里相关(r=0.556,P=0.001)。SLE患者KIR2DL4的转录水平有所提高,但是差异没有统计学意义[(1.38±3.46)vs.(0.35±0.78),P=0.558]。结论妊娠合并SLE患者CD4+T细胞中ITGAL、PRF1和CD70存在过表达。CD40LG与ITGAL和PRF1之间的联系密切,因此推断它可能与SLE的发病机理有关。这些基因的表达水平与全基因组DNA甲基化水平以及多种甲基化相关酶之间的协同联系,支持了表观遗传学机制与ITGAL,PRF1,CD40LG的异常调节有关。
Objective The study aims to discuss the expression and epigenetic mechanism of DNMTs and MBDs in pregnancy patients with systemic lupus erythematosus.Methods CD4^+T cells were isolated from random ly selected 31 single pregnant women with SLE and 30 healthy single pregnancy female volunteers.The enzyme linked immunosorbent assay(ELISA)was used to detect deoxy methylcytosine in DNA cells.The transcriptional level of ITGAL,PRF1,KIR2DL4,CD70,CD40LG,DNMT1,DNMT3A,DNMT3B,MBD2 and MBD4 were quantified by real-time quantitative polymerase chain reaction(RT-PCR).Results he pregnancy patients with SLE increased the transcriptional leveI of ITGAL(8.57±21.51 vs.7.18±9.36,P=0.004 6),PRF1(21.59±24.28 vs.10.37±11.25,P=0.011 7),and CD70(1.48±1.63 vs.0.71±0.26,P=0.005 9).There was a signifi cant positive correlation between CD40LG and ITGAL transcription level(r=0.468,P=0.005),and there was a significant correlation between PRF1 and CD40LG(r=0.556,P=0.001).The transcriptional level of KIR2DL4 in SLE patients was improved,but there was no statistical significance(1.38±3.46 vs.0.35±0.78,P=0.558).We observed that these genes are closely related to the global DNA methylation and the expression of most DNA methylation related genes,especially ITGAL,PRF1 and CD40LG.Conclusions The expression of ITGAL,PRF1 and CD70 in the CD4^+T cells of SLE patients with pregnancy are overexpressed.The close connection be tween CD40LG and ITGAL and PRF1 makes us infer that it may be related to the pathogenesis of the disease.The synergistic relationship between the expression level of these genes and the DNA methylation level of the global DNA and various methylation related enzymes supports that the epigenetic mechanism is related to the abnormal regulation of ITGAL,PRF1 and CD40LG.
作者
刘恩令
周玉秀
刘铮
李君
张冬红
蔡朝辉
陈梅
郑寰宇
李月红
LIU Enling;ZHOU Yuxiu;LIU Zheng;LI Jun;ZHANG Donghong;CAI Zhao hui;CHEN Mei;ZHENG Huanyu;LI Yuehong(The department of Obstetrics and Gynecology,Tangshan Gongren Hospital Affiliated to Hebei Medical University,Tangshan 063000,China)
出处
《实用医学杂志》
CAS
北大核心
2019年第2期233-237,共5页
The Journal of Practical Medicine
基金
河北省科技厅计划项目(编号:162777190)
