基于HMGB1/Treg免疫负调控效应探讨益气温阳解毒法对脓毒症的保护机制

项目名称： 基于HMGB1/Treg免疫负调控效应探讨益气温阳解毒法对脓毒症的保护机制

项目编号： No.81473613

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王蕾

作者单位： 中国中医科学院广安门医院

项目金额： 72万元

中文摘要： 免疫功能紊乱，尤其是免疫抑制和免疫负调控效应是脓毒症发病的关键环节。益气温阳解毒法在前期研究中显示出对脓毒症的器官保护作用和免疫调理的潜在优势，课题组结合现代分子免疫进展，提出益气温阳解毒法通过对脓毒症免疫过度反应与免疫抑制的失衡进行调节，尤其是干预以HMGB1/Treg为介导的免疫负调控通路是其可能的作用靶点的假说。本课题将从器官保护、T细胞功能分化、T效应细胞免疫无能、负调控因子表达、Treg细胞增殖与凋亡、HMGB1与Treg受体的相互作用等多层面，探讨益气温阳解毒法及其子方治疗脓毒症的疗效与HMGB1/Treg通路的免疫负调控机制的内在关联，揭示其治疗脓毒症的分子免疫机制,为进一步阐明扶正解毒理论治疗脓毒症的科学内涵提供客观依据，为危重症的中医治疗提供新思路。同时，通过拆方研究，观察扶正、解毒法在脓毒症免疫状态中起效的时相和靶点差异，从一个方面诠释中医治法的物质基础。

中文关键词： 脓毒症；益气温阳解毒；免疫抑制；高迁移率族蛋白B1；调节性T细胞

英文摘要： The mechanism of sepsis is very complicated characterized with immune function disorder especially the key role of immune suppression and negative immune regulation. The effective method included Tonifying Qi warming Yang and cleaning the heat had been used clinically for many years. The representative formula Shen Fu Huag (SFH) showed the protective effect on septic organs downstream the expression of anti-infection cytokine.After reviewing the current literature, we hypothesized that the method included Tonifying Qi warming Yang and cleaning the heat might regulate the imbalance of immune over-reaction and immune suppression especially acting on the target pathway typically regulated through HMGB1/Treg immune negative regulation. This proposed project will try to explore the homeostasis of human immune function through lung protection, T cell activation, inflammation cell activation, Treg cell proliferation and apoptosis, HMGB1 and Treg expression. The success of this study will provide a new Traditional Chinese Medicine (TCM) approach to the critical care and provide the evidence for the TCM theory -- Nourish and Clean.

英文关键词： Sepsis;Method of Tonifying Qi Warming Yang and Clearing Heat;Immune Suppression;High Mobility Group Box-1;Regulatory T cell