电针通过miR-128-3p调控脑淋巴系统VEGFR-3信号通路延缓AD病理进程的机制研究

批准号:
82004465
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王临梅
依托单位:
学科分类:
中医针灸学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王临梅
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中文摘要
β淀粉样蛋白(Aβ)的生成与清除失平衡是AD起病与发展的重要影响因素,减少Aβ在脑内积聚是防治AD的关键策略。最新研究报道硬脑膜内存在淋巴管结构,对Aβ清除发挥重要作用,可作为干预AD病理进程新靶点。我们预实验发现,电针百会、肾俞穴可改善6月龄APP/PS1小鼠硬脑膜淋巴管结构损伤和引流功能的下降,促进脑内Aβ清除。为进一步深入探索电针作用的分子机制,基于最新研究成果,采用生物信息学方法,将特异性影响硬脑膜淋巴管生成的VEGFR-3信号通路,及其上游调控因子miR-128-3p作为干预靶标,通过使用转基因模式小鼠及分子生物学方法探讨:①电针百会、肾俞穴对AD病理进程产生的延缓作用;②电针对硬脑膜淋巴管结构和功能的保护作用;③电针对硬脑膜淋巴管作用的靶点及分子机制。本研究可为明确电针作用机理提供新的实验依据,并为寻找AD的特异性治疗靶点和干预手段,提供新思路。
英文摘要
The imbalance between production and clearance of β-amyloid (Aβ) is believed to be the key step in the onset and development of Alzheimer’ s disease (AD). Therefore, reducing Aβ accumulation in the brain is an important therapeutic strategy for AD. Recent studies have reported that there are lymphatic vessels in the dura mater, which play an important role in the clearance of Aβ. This can be used as a new target to interfere with the pathological process of AD. Our preliminary experimental results found that electroacupuncture (EA) applied at Baihui (GV20) and Shenshu (BL23) could maintain the structural integrity of meningeal lymphatics and improve the drainage function of 6-month-old APP/PS1 mice, which finally reduced the deposition of Aβ in the brain. In order to explore the mechanism of EA, based on the latest research results, the VEGFR-3 signal pathway and miR-128-3p, which specifically affect the formation of meningeal lymphatics, were selected as the intervention target. Using the transgenic model mice and molecular biological methods, it will be clear: ① the effect of EA at Baihui and Shenshu on postponing AD pathological process; ②The effect of EA on protecting the structure and function of meningeal lymphatics; ③the target and molecular mechanism of EA affect on meningeal lymphatics. This research can provide new experimental and theoretical basis for elucidating the mechanism of EA and provide new ideas for finding specific therapeutic targets for AD.
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DOI:10.1080/02648725.2023.2177046
发表时间:2023
期刊:Biotechnology and Genetic Engineering Reviews
影响因子:--
作者:Shenxu Chen;Linmei Wang;Ying Yuan;Yunfan Wen;Shi Shu
通讯作者:Shi Shu
国内基金
海外基金
