miRNAs与寻常型银屑病易感基因的相关性研究及竹黄颗粒对其的干预作用

Psoriasis vulgaris is a polygenic disease.Inflammation, excessive proliferation of epidermal cells and the immunological abnormality is the central link in its incidence.The study of the genome-wide association analysis for susceptibility genes of psoriasis vulgaris have shown that HLA-Cw6 is the MHC susceptibility genes which strongest associated with the immune response ,IL12B and IL23R is the non-MHC susceptibility genes which closely associated with the inflammatory response, LCE3A and LCE3D is the susceptibility gene which impact on the process of psoriasis.. MiRNAs participate in an important link in the life course, involved in cell differentiation, regulation of cell proliferation and apoptosis, involved in immune response and regulation of gene expression.there are specific differences in expression of miRNAs in psoriasis.. This subject intends to study the correlation between miRNAs and the psoriasis susceptibility genes and to explore the function of miRNA from the relationship between the levels of miRNAs and psoriasis susceptibility genes.And to observe the intervention effect on their expression by ZhuHuang Granule and to explore the critical role of Chinese medicine treatment of psoriasis.

寻常型银屑病是一种多基因遗传疾病。炎症、表皮细胞过度增殖和免疫学异常是其发病的中心环节。全基因组关联分析对寻常型银屑病易感基因研究显示HLA-Cw6是与银屑病免疫反应相关最强的MHC易感基因，IL12B和IL23R是两个与炎症反应密切关联的非MHC易感基因，LCE3A和LCE3D编码异常角质化包膜蛋白，是影响银屑病角化过程的易感基因。miRNAs参与生命过程中的重要环节，具有参与细胞分化、调节细胞增殖和凋亡、参与免疫应答和调控基因表达等作用，miRNAs在银屑病中存在特异性差异表达。本课题拟研究寻常型银屑病患者血清中miRNAs与HLA-Cw6、IL12B、IL23R、LCE3A和LCE3D表达的相关性，从miRNAs与银屑病易感基因的关系层面探讨miRNAs的功能，同时观察中药竹黄颗粒对它们表达的干预作用，探索中医药治疗银屑病的关键作用靶点，为中医药防治银屑病提供理论与实验依据。

寻常型银屑病是一种多基因遗传疾病。炎症、表皮细胞过度增殖和免疫学异常是其发病的中心环节。全基因组关联分析对寻常型银屑病易感基因，结合高通量miRNA芯片结果，从miRNA-基因-细胞因子层面研究银屑病的发病机制，以及探讨竹黄颗粒对其干预作用。通过CD4+T淋巴细胞和PBMCs miRNA芯片筛选、RT-qPCR、MTT、ELISA、蛋白芯片等实验技术手段，以及gene-miRNA在线工具预测等多种软件的应用，与临床病人的PASI评分进行结合，筛选出银屑病CD4+T淋巴细胞和PBMCs细胞中差异表达的miRNAs，并对差异表达显著的miRNAs进行了进一步研究，如miR-146a、miR-99a、miR-155等与PASI评分关系密切，可能在银屑病发病过程中发挥重要作用。此外，血清和血浆中细胞因子的表达也是关注的重点，多种细胞因子表达升高，少数细胞因子表达降低，与PASI评分密切相关。竹黄颗粒的干预作用机制研究中，一方面影响miRNAs的表达，另一方面可有效降低细胞因子的含量。本课题为银屑病gene-miRNA-细胞因子的研究提供了有效的依据，为银屑病发病机制的阐述及早期诊断提供了新的思路，为下一步开展miRNA靶基因功能研究提供了参考。