原发免疫性血小板减少症“脾肾气火相关”病机与Breg相关性研究

原发免疫性血小板减少症（ITP）发病缘于机体对自身抗原的免疫失耐受，涉及B细胞、T细胞、抗原呈递细胞、骨髓巨核细胞之间的相互作用，是复杂的免疫网络紊乱的结果。其发病机制已由简单模式转变为复杂模式，与课题组提出的ITP“脾肾气火相关”中医发病学说高度契合。本学说以整体观念为指导，将脏腑辨证与气血有机结合，体现了中医“联系”和“变化”的思想，但其具体分子机制不明。鉴于最新发现的Breg（调节性B细胞）可在体液免疫和细胞免疫的不同环节发挥作用，在ITP免疫紊乱中的地位较Treg更重要，因此，本研究拟在前期研究基础上，采用分子生物学技术，以方示理，从体内、体外实验两个方面，拆方研究有效制剂健脾滋肾泻火方对Breg数量、功能及其BLNK/CD40信号通路关键分子和靶基因表达的影响，多层次探讨ITP“脾肾气火相关”病机与Breg介导的免疫紊乱之间的关系，揭示ITP“脾肾气火相关”中医病机的免疫学机理。

The body's own immune antigen losing tolerance is the main pathogenesis of primary immune thrombocytopenia (ITP),involving the interrelation of B cells,T cells,antigen-presenting cells and the bone marrow megakaryocytes. ITP is the result of a complex disorder of the immune network. Its pathogenesis is a paradigm shifting from simple to complex patterns, which is identical with the ITP’s TCM pathogenesis-" correlation of qi-fire between Spleen and Kidney " advanced by ourresearch group. The theory is guided by the holism and integrate syndrome differentiation of viscera and qi-blood. It reflects the traditional Chinese medicine ideology of "contact" and "change",but the specific molecular mechanism is unknown. the latest findings showed that Breg (regulatory B cells) can also play a role at different stages of humoral and cellular immunity, whose role in immune disorders of ITP is more important than that of Treg. Therefore, Based on previous study,we will explore the principle through prescription of traditional Chinese medicine by using molecular biology technique. This study intend to observe the effects of "invigorating spleen, nourishing kidney and reducing fire" prescription and its portion on the number and function of Breg, and the expression of critical molecules and target gene of the BLNK/CD40 signaling pathway in ITP mouse mode by in vivo and in vitro experiments. We want to study the relationship between ITP’s "correlation of qi-fire between Spleen and Kidney" pathogenesis and immune-mediated disorders among Breg at different levels, thus revealing the immunological mechanism of ITP’s TCM pathogenesis-" correlation of qi-fire between Spleen and Kidney ".