中文摘要
系统性红斑狼疮(SLE)是一种累及多器官的自身免疫性疾病。近年来越来越多研究发现MeCP2/IRAK1信号通路异常时引起TNF-α、INF-α等因子的过度表达,导致SLE的发病。课题组前期研究发现解毒祛瘀滋阴方可以有效降低SLE患者体内紊乱的细胞因子、自身抗体水平,其治疗SLE的作用机制可能是通过调整MeCP2/IRAK1通路来实现的,那么该方剂在此信号通路中如何起作用,作用的分子机制是什么,均有待于实验进行验证。.本项目通过体外、体内实验,给予解毒祛瘀滋阴方作用于Jurkat细胞、Raw264.7单核巨噬细胞和MRL/lpr狼疮小鼠,治疗后分别检测MeCP2、TNF-α、TLR7、TLR9、NF-kB、MyD88、IRAK1蛋白及mRNA水平。深入探讨该方剂治疗SLE的机制在于调节紊乱的MeCP2/IRAK1通路,从而纠正CD4+T细胞和IRAK1蛋白激酶过度激活而引起治疗作用。
英文摘要
Systemic Lupus Erythematosus (SLE) is an autoimmune disease involving multiple organ system. In recent years, more and more studies found when the MeCP2 / IRAK1 pathway is abnormal, it can cause the gene’ excessive expression such as TNF-α,IFN-α,resulting in the pathogenesis of SLE. Our research group study identified Jiedu Quyu Ziyin Decoction can effectively reduce the disorder of cytokine and autoantibody levels the SLE patients. Its mechanism for treating SLE may be achieved by adjusting the MeCP2/IRAK1 signaling pathway, then the prescription how to play a role in this signaling pathway, what is the molecular mechanism of action, are subject to be verified in experiment. This project through in vitro and in vivo experiment, giving the Jiedu quyu ziyin Decoction effect on Jurkat T cell and mouse macrophage RAW264.7 and MRL/lpr mice. After treatment, respectively to detect the protein of TNF-α,MeCP2,TLR7, TLR9,NF-kB, MyD88, IRAK1 and their mRNA expression levels. Further explore the mechanism of Jiedu Quyu Ziyin Decoction’s in the treatment of SLE lies in adjusting the disorder of MeCP2 / IRAK1 signaling pathways , correcting the excessive activation of CD+4T cells and IRAK1 protein kinase and then play a role in the treatment.
