新型活性单体芍药苷-6-氧-苯磺酸酯在类风湿关节炎免疫应答与炎症中的调控作用

白芍总苷（TGP）是我国第一个批准上市治疗类风湿关节炎（RA）抗炎免疫调节药。新型活性单体芍药苷-6-氧-苯磺酸酯（代号CP-25）来自于TGP有效活性成份芍药苷（Pae）结构修饰，已申请专利。与Pae相比，CP-25绝对生物利用度高，具有良好抗炎和免疫调节活性。树突细胞（DCs）递呈抗原活化T细胞，T细胞与B细胞和FLS相互作用，活化B细胞，诱导FLS炎性转变，参与RA免疫应答和滑膜炎症。CP-25对RA免疫应答和滑膜炎症具有怎样调控作用？是否通过调节DCs、T、B细胞和FLS功能及细胞间相互作用发挥其调控作用？国内外未见文献报道。本项目拟以RA患者和动物模型为研究对象，通过激动剂、拮抗剂和siRNA等干预，采用不同分子生物学技术，探讨CP-25对DCs、T、B细胞和FLS功能及细胞间相互作用的调节，并揭示CP-25调控机制。为把CP-25开发为独立自主知识产权新的原创药物打下坚实基础。

Total glucosides of paeony (TGP) is the first anti-inflammatory immune regulatory drug in treatment for rheumatoid arthritis (RA) approved in China. New active monomers paeoniflorin - 6 - oxygen - benzene sulfonic acid ester (code is CP - 25) come from the structure modification of paeoniflorin (Pae), which was the effective active ingredients of TGP, and the patents of CP – 25 has been applied. Compared with Pae, CP – 25 has good anti-inflammatory and immune regulation activity, and the absolute bioavailability of CP – 25 is high. In RA immune response and synovial inflammation, it was found that dendritic cells (DCs) activated T cells by presenting the antigen to T cell, the interaction between T cell and B cell or FLS, and B cells were activated, inflammatory change of FLS was induced. how does CP - 25 regulate immune response and synovial inflammation in RA? Whether does CP – 25 play its regulation function through the adjustment of DCs, T and B cells and FLS function and cell interaction? No reports in the literature have seen at home and abroad. In this project, RA patients and animal model intend to be as research object, agonist, antagonist and siRNA will be used as intervention, and different molecular biology technology will be utilized. The regulation of CP - 25 on the functions and cell interaction of DCs, T and B cells and FLS will be investigated, and the regulation mechanism of CP - 25 will be revealed. This project will offer a solid foundation for developing CP - 25 as the independent intellectual property rights of new original drugs.