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IL-2通过抑制调节性T细胞凋亡减轻热射病的机制研究

IL-2通过抑制调节性T细胞凋亡减轻热射病的机制研究
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  • 批准号:81501642
  • 批准年度: 2015年
  • 学科分类:多脏器衰竭(H1502) |
  • 项目负责人:胡婕
  • 负责人职称:主治医师
  • 依托单位:中国人民解放军总医院
  • 资助金额:18万元
  • 项目类别:青年科学基金项目
  • 研究期限:2016年01月01日 至 2018年12月31日
  • 中文关键词: IL-2;调节性;凋亡;减轻;热射病
  • 英文关键词:heatstroke;regulatory T cells;Interleukin-2

项目摘要

中文摘要

热射病发病率逐年升高,死亡率60%以上。过度激活炎症反应是其重要的发病机制,调节性T细胞(Tregs)在炎症性疾病中发挥了重要作用,白介素2(IL-2)可通过抑制Tregs凋亡治疗炎症性疾病。但Tregs参与热射病及IL-2在治疗热射病中的作用及机制无人研究。前期工作发现IL-2下降、脾脏Tregs凋亡增加、数量减少。本项目建立热射病小鼠模型,将肝肾功、病理、死亡率及炎症反应作为评价疾病严重程度的参数。分别研究过继性转移Tregs或条件性敲除Tregs对疾病严重程度的影响,明确Tregs在热射病中的作用。采用多色荧光标记的流式细胞技术、免疫荧光技术等阐明IL-2通过何种机制减轻热射病,并优化IL-2的治疗方案。从而提出并验证IL-2通过抑制Fas介导的Tregs凋亡减轻热射病的科学假说。本项目的完成不仅使热射病发病机制研究获得新的突破,而且为临床应用IL-2治疗热射病奠定了坚实的理论基础。

英文摘要

Heatstroke morbidity is growing higher and mortality is more than 60%. Overwhelming systemic inflammatory response is one of the important pathogenesis. Regulatory T cells (Tregs) was proved to play an important role in inflammatory related diseases. Interleukin-2 could attenuate inflammatory related diseases via inhibiting Tregs apoptosis.However, whether Tregs is involved in heatstroke and IL-2 could protect against heatstorke and its potential mechanism were unknown. Our group has found decrease of serum IL-2 and splenic Tregs and increase of Treg apoptosis. In this research,we firstly established heatsroke mouse model and define illness severity as hepatic and renal function,pathology,mortality and inflammatory response; secondly, we verified whether Tregs were invovled in heatstroke via detection of illness severity in the situation of adoptive transfer or conventional depletion of Tregs; thirdly, we clarified the the attenuation of IL-2 in heatstroke and its potential mechanism by the way of multiple color flow cytometry, single photon fluorescence imaging,and etc.; at last, we optimized theraputic protocal of IL-2. With all the problems solved,our research could for the first time reveal that Tregs was involved in heatstroke and IL-2 could attenuate heatstroke via inhibiting Fas-mediated Treg apoptosis,which might provide new clue to research on mechanisms of heatstroke and IL-2 therapy in heatstroke and highlight its application in clinical practice.

评估说明

    国家自然科学基金项目“IL-2通过抑制调节性T细胞凋亡减轻热射病的机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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