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从AMPK/mTOR通路探讨高糖诱导血管衰老的机制及益气活血药的干预作用

从AMPK/mTOR通路探讨高糖诱导血管衰老的机制及益气活血药的干预作用
  • 导航:首页 > 科学基金
  • 批准号:81673822
  • 批准年度: 2016年
  • 学科分类:中西医结合临床基础(H2902) |
  • 项目负责人:雷燕
  • 负责人职称:研究员
  • 依托单位:中国中医科学院医学实验中心
  • 资助金额:52万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: AMPK/mTOR;衰老;益气;活血;干预
  • 英文关键词:vascular aging; AMPK/mTOR Pathway;Yiqi Huoxue Chinese Herbal Medicine ;high glucose;mechanism rese

项目摘要

中文摘要

血管衰老是糖尿病血管并发症的基本病理改变。腺苷酸活化蛋白激酶(AMPK)和哺乳动物雷帕霉素靶蛋白(mTOR)均与衰老及糖代谢密切相关,但AMPK/mTOR通路在糖尿病诱导的血管衰老中作用机制不明。高糖诱导的血管衰老及AMPK/mTOR通路变化均与氧化应激关系密切,且AMPK可通过PPARγ、p53调控细胞寿命。前期研究发现,益气活血药人参三七川芎提取物可抑制氧化应激并调节PPARγ与p53通路从而延缓小鼠血管衰老,其是否通过调节氧化应激下AMPK/mTOR通路的改变延缓糖尿病引发的血管老化尚不明确。本研究建立高糖环境下的血管衰老小鼠与细胞衰老模型,采用RNA干扰和基因转染技术实现衰老细胞AMPK基因沉默和mTOR过表达,探讨AMPK/mTOR通路对高糖诱导的血管衰老的影响,明确益气活血药通过AMPK/mTOR通路延缓血管老化的作用机制,阐明益气活血药祛瘀生新、通脉活络的科学内涵。

英文摘要

Vascular aging belongs to the basic pathological change of vascular complications of diabetis. Adenosine Monophosphate Activated Protein Kinase (AMPK) / mammalian target of rapamycin (mTOR) pathway is closely associated with aging and glycometabolism, but the effect of AMPK/mTOR pathway is not clear in the vascular aging induced by diabetes. High glucose-induced vascular senescence and the change of AMPK pathwayare closely related to oxidative stress and AMPK could regulate the cell life by PPAR gamma and p53. Our previous studies found that Radix Ginseng, Radix Notoginseng and Rhizoma Chuanxiong extracts, one of Yiqi huoxue Chinese Herbal Medicine, could delay the vascular aging of the mice by inhibiting the oxidative stress and regulating the PPAR gamma and p53 pathway. But the functional mechanism of this Chinese Herbal Medicine remained unclear whether it could regulate the change of AMPK/mTOR pathway in the oxidative stress in order to delay the vascular aging induced by diabetes. In this study we set up the models of the vascular aging mice and cell senescence in high-glucose environments, and realize gene silencing of AMPK and overexpression of mTOR on senescent cells by RNA interference gene and transfection technology in order to discuss the action of AMPK/mTOR pathway for the vascular senescence induced by high glucose, ascertain the mechanism of this medicine to delay vascular aging by AMPK/mTOR pathway and illuminate the scientific connotation of yiqi huoxue Chinese Herbal Medicine on removing stasis and promoting coronary circulation.

评估说明

    国家自然科学基金项目“从AMPK/mTOR通路探讨高糖诱导血管衰老的机制及益气活血药的干预作用”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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