基于EB病毒-易感基因间表观遗传对话探讨解毒祛瘀滋阴方治疗SLE作用机理

系统性红斑狼疮（SLE）是一种多器官受累、预后差的疾病。EB病毒感染作为激发因素，通过表观遗传途径（DNA甲基化、组蛋白修饰、MicroRNA），引起SLE易感基因（HLA-DRB1、BLK、TNFSF4、STAT4、ETS1、TET3）表达异常，诱导SLE发病。解毒祛瘀滋阴方可缓解SLE病情，提高生存质量。本项目先检测EBV（+）SLE患者潜伏膜蛋白1（LMP-1）和易感基因表达的相关性；再将携带LMP-1基因慢病毒感染EBV（-）SLE患者T、B细胞，干预培养后检测易感基因表达量和表观遗传调控水平（DNA甲基化、组蛋白修饰、miRNA）；最后将LMP-1慢病毒质粒注射到MRL/lpr狼疮鼠体内，验证EBV是否通过表观遗传途径影响易感基因表达，同时观察中药对其干预作用。 从“EBV与SLE易感基因间表观遗传对话”研究解毒祛瘀滋阴方治疗SLE作用机理。

Systemic lupus erythematosus(SLE) is an autoimmune disease with multi-systemic organs injury and bad prognosis. EB virus, as a trigger, maybe result in SLE relative susceptible genes abnormal expression through epigenetic regulation (DNA methylation, modifications of histone, microRNAs) . Our previous studies confirmed that Jieduquyuziyin decocotion can obviously lighten SLE disease activity and improve patients' life quality. The main contents including: Firstly, the relationship between gene expression of latent membrane protein 1 of SLE patients with positive EB virus maker and susceptible genes was detected. Secondly, T and B lymphocytes of SLE patients with negative EB virus maker were transfected by lentivirus with LMP-1gene and cultured with different drugs. Expression of epigenetic regulation relative genes (DNA methylation, modifications of histone, microRNAs) and susceptible genes were detected. Finally, lentivirus with LMP-1gene were injected into MRL/lpr mice and confirmed whether susceptible gene expression were affected through epigenetic mechanism or not. The effects of Jieduquyuziyin decocotion on them were also detected. The aim of this study was to investigate the mechanism of Jieduquyuziyin decocotion treating SLE based on epigenetic dialogue between EB virus and susceptible genes.