中文摘要
发掘深静脉血栓(DVT)有效治疗方法的难点在于其发病机制的复杂性,其中免疫机制是研究热点之一。本项目在前期创新性发现DVT中T细胞亚群失衡与血管内皮细胞(VEC)损伤和DVT病情演变密切相关,并被化瘀清热利湿中药逆转基础上,拟重点探讨T细胞失衡的始动因素和药物作用靶点。根据DVT小鼠存在树突状细胞(DC)亚群失衡、化瘀清热利湿中药调控Jak/STAT信号通路而影响DC亚群功能等预实验结果,结合DC启动并调控T细胞分化与应答免疫学理论,推测DC功能改变是DVT中T细胞亚群失衡的根源和化瘀清热利湿法干预的靶点。重点探讨DVT中DC对T细胞失衡的影响、Jak/STAT信号通路对DC的调控,以及化瘀清热利湿法通过Jak/STAT途径调控DC的作用。预期结果将阐释化瘀清热利湿法靶向Jak/STAT信号通路调节DC功能治疗DVT的关键机制,丰富中医学“瘀热病机理论”科学内涵,为治疗提供新的靶点与途径。
英文摘要
Deep vein thrombosis (DVT) does serious harm for patients’ health, and the development of theraputic method is meaningful in this field. The pathogenesis of DVT is multiple, and the immunologic mechanism is a hot point in recent years. In our previously study, it was found that T-cell paradigm shift is involed in DVT; however, the initial factor and mechanism of this phenomenon remain unclear. Dendritic cells (DCs) play a vital role in initiating and regulating T-cell immune response, and Jak/STAT signaling pathway is cricial for development of DC’s differentiation and funcuntion. Accoding to the leading edge of communication between DCs and T-cells, and base on the findings of our pre-experiment that there is dysfunction of DC in DVT mice and the TCM method of Huyuqingrelishi has regulatory effect on it, it was hypothesized that the subsets differentiation and funcion of DCs are involved in the T-cell subsets shift in DVT, and DCs may be the effective therapeutic target of the TCM method of Huyuqingrelishi for treating DVT. The current research will focus on the pathogenic role of DC in DVT and the regulatory effect of Huyuqingrelishi on it via targeting Jak/STAT signaling pathway. The findings of the current research will further elucidate the immunologic mechanism of DVT, enrich the scientific meaning of “Yure Theory” in TCM, and offer novel therapeutic method and target for the clinic.
