摘要
目的 探讨miRNA-146a通过Toll样受体/核因子κB(TLRs/NF-κB)信号通路参与系统性红斑狼疮(SLE)发病机制及其临床意义.方法 收集2023年1月～2023年12月于我院住院的30例SLE患者及同时间段于我院体检中心进行健康体检者20例.采集患者的基本信息、临床表现、疾病活动检验参数并进行SLEDAI评分.应用实时-定量反转录聚合酶链反应(qRT-PCR)法测定 miRNA-146a,ELISA 法测 IL-1β、IL-6、TNF-α 水平,qRT-PCR 法和蛋白免疫印迹法测 IRAK-1、TRAF-6、NF-κB p65 水平,研究三者之间关系.结果 SLE活动组和SLE缓解组患者中miRNA-146a表达水平均明显低于正常对照组(P=0.0012,P=00492);相对于缓解组SLE患者,活动组SLE患者miRNA-146a表达水平明显降低;SLE患者与正常对照组IL-1β、IL-6、TNF-α等炎症因子水平比较,SLE患者表达水平明显高于正常对照组(P=0.0013,P=0.0014和P=0.0288);SLE患者与正常对照组miRNA-146a靶基因表达水平比较,两组外周血单个核细胞中miRNA-146a的3个靶基因表达水平存在差异,SLE患者组中IRAK、TRAF6、NF-κB p65 mRNA表达水平显著高于正常对照组(P＜0.0001,P＜0.0001和P=0.0002),且蛋白表达水平亦高于正常对照组.结论 miRNA-146a通过调控Toll样受体/核因子κB信号通路参与SLE发病.
Abstract
Objective To investigate whether miRNA-146a participates in the pathogenesis of systemic lupus erythematosus(SLE)through toll-like receptors/nuclear factor κB(TLRs/NF-κB)signaling pathway and its clinical significance.Methods Thirty SLE patients admitted to our hospital and 20 healthy individuals undergoing health examinations at our hospital from January 2023 to December 2023 were included.Basic patient information,clinical manifestations,disease activity test parameters,and SLE Disease Activity Index(SLE-DAI)scores were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was applied to measure miR-NA-146a levels,while enzyme-linked immunosorbent assay(ELISA)was applied to measure IL-1β,IL-6,and TNF-α levels.QRT-PCR and protein immunoblotting was applied to measure the levels of IRAK-1,TRAF-6,and NF-κB p65.The relationships between these factors were explored.Results The expression of miRNA-146a in active and stable SLE patients was significantly lower than that in the normal control group(P=0.0012,P=0.0492).Moreover,the expression of miRNA-146a in active SLE patients was significantly lower compared to stable SLE patients.In comparison to the normal control group,SLE patients showed significantly higher levels of inflammatory factors such as IL-1β,IL-6,and TNF-α(P=0.0013,P=0.0014,and P=0.0288,respectively).Comparison of miRNA-146a target gene expression levels be-tween SLE patients and the normal control group revealed differences in the expression levels of three target genes in peripheral blood mono-nuclear cells.In the SLE patient group,the mRNA expression levels of IRAKI,TRAF6,and NF-κB p65 were significantly higher than those in the normal control group(P＜0.0001,P＜0.0001,and P=0.0002,respectively),and the protein expression levels were also higher than those in the normal control group.Conclusion miRNA-146a is involved in the pathogenesis of SLE by regulating the Toll-like receptor/nuclear factor-κB signaling pathway.
基金项目
潍坊市卫生健康委科研项目(WFWSJK-2022-190)
潍坊医学院研究生科研创新基金()
NETL
NSTL
万方数据