脓毒症是目前全世界所面临的严峻医学问题。申请人前期通过CD45高通量筛选模型首次发现黄芪皂苷能够显著激活CD45蛋白酪氨酸磷酸酯酶，从而增强细胞免疫功能。基于黄芪皂苷抗脓毒症疗效已明确，本项目以"黄芪皂苷激活CD45 PTPase影响T淋巴细胞免疫反应介导抗脓毒症作用”为科学假设，拟在CD45-/-基因敲除小鼠模式动物脓毒血症模型和CD45-/-基因敲除小鼠Th1、Th17和Treg体外分化模型，采用流式细胞术和实时荧光定量PCR等技术，从T淋巴细胞亚群增殖、细胞因子分泌、分化和CD45信号转导通路关键信号蛋白的磷酸化状态及转录因子表达等多个层面，研究CD45分子影响T细胞亚群分化改善脓毒症的效应机制，探索脓毒症免疫治疗可能的治疗靶点。并以CD45PTPase小分子激活剂（黄芪皂苷）为探针，揭示细胞亚群分化和CD45信号途径变化规律，为黄芪临床应用脓毒症治疗、传承与创新奠定理论基础。

Sepsis is a major clinical challenge in modern medicine.Through high-throughput screening model of CD45 PTPase, our previous study firstly reported that astragaloside could significantly activate CD45 PTPase, thus to enhance cellular immunity. Considering the well-established in vivo anti-sepsis effects of astragaloside,we then hyperthesize that the astragaloside protects against sepsis through via influencing T lymphocytes immune responses which induced by CD45 PTPase.This proposed study will also further investigate the mechanism of CD45 PTPase influencing T lymphocytes differentiation in sepsis and explore therapeutic target of sepsis. Cecal ligation and puncture (CLP)-induced sepsis model in CD45-/- gene knockout mice ,in vitro T cell subset differentiation (Th1,Th17 and Treg) will be used.The immune reaction will be monitors from the aspects of proliferation, cytokine production, phosphorylated CD45 signal molecules and expression of transcription factor. Meanwhile,In order to further explore the mechanistic pathways of astragaloside on T cell subsets differentiation and CD45 signal molecules,The Astragaloside was used a probe of CD45PTPase small molecule activator,Collectively, the proposed study will explore the new anti-sepsis mechanism of astragaloside and enhance the theoretical foundation for anti-sepsis immunotherapy of Astragalus, inheritance and innovation and new drugs research.