通窍明目IV号通过miR-466调节PTEN/AKT/mTOR自噬通路治疗青光眼视神经损害的机制研究
批准号:
82004425
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王丽媛
依托单位:
学科分类:
中医眼科学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王丽媛
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中文摘要
青光眼是常见的视神经退行性疾病,其发病机制复杂,导致的视神经损害尚无特效治疗方法。祖国医学认为,阴阳失调,肝气郁结,导致目中经脉不利,玄府闭塞是青光眼发生的主要原因。自噬维持着细胞内稳态,受多种miRNA调控,其动态平衡与中医的阴阳理论相呼应,其失衡亦与青光眼的发生发展有关。本课题组前期研究发现,通窍明目IV号能够有效缓解青光眼模型大鼠视神经损害,并筛选了治疗后大鼠视网膜差异性表达的miRNA,其中高表达的miR-466与PTEN序列相对应,而PTEN是自噬调控的关键基因。基于这一结果,本课题组旨在通过体内、体外实验,采用现代生物学技术,应用miRNA抑制剂、模拟剂及通路抑制剂,从组织形态、基因转录调控、蛋白表达等多个层次,深入研究通窍明目4号通过miR-466调节PTEN/AKT/mTOR自噬通路,进而发挥视神经保护作用的机制,为青光眼寻找新的治疗靶点,为中医药治疗青光眼提供理论依据。
英文摘要
Glaucoma is a common optic nerve degenerative disease, with complex pathogenesis and there is no effective treatment for its optic neuropathy. According to traditional Chinese medicine, the main cause of glaucoma is stasis of the meridians and orifices in the eyes caused by Yin-Yang imbalance and liver Qi stagnation. Autophagy maintains cellular homeostasis and is regulated by various miRNAs. The dynamic balance of autophagy corresponds to the Yin-Yang theory of traditional Chinese medicine, and its imbalance is also related to the occurrence and development of glaucoma. In our previous study, we found that Tongqiao Mingmu IV decoction can effectively alleviate the optic neuropathy of glaucoma model rats, and screened the differentially expressed miRNAs in the retinas of rats after treatment. The high expressed miR-466 corresponds to PTEN sequence, and PTEN is a crucial gene in autophagy regulation. Based on this result, our research group adopt modern biological technology in vivo and vitro, applies miRNA inhibitors, simulators and pathway inhibitors, from multiple aspects includes organization form, gene transcription regulation, protein expression, to investigate the mechanism of Tongqiao Mingmu IV decoction protect optic nerve by regulates the PTEN/AKT/mTOR autophagy pathway through miR-466, looking for new therapeutic targets for glaucoma, and providing a theoretical basis for the treatment of glaucoma with traditional Chinese medicine.
期刊论文列表
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DOI:10.19378/j.issn.1003-9783.2022.04.012
发表时间:2022
期刊:中药新药与临床药理
影响因子:--
作者:付晋;王丽媛;董霏雪;孙河
通讯作者:孙河
DOI:10.3389/fcell.2021.793638
发表时间:2021
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Wang L;Yu T;Zhang X;Cai X;Sun H
通讯作者:Sun H
DOI:10.1371/journal.pone.0282866
发表时间:2023
期刊:PloS one
影响因子:3.7
作者:
通讯作者:
DOI:--
发表时间:2022
期刊:中华中医药杂志
影响因子:--
作者:王丽媛;于天洋;董霏雪;赵爽;樊晓瑞;孙河
通讯作者:孙河
DOI:10.1002/ar.25060
发表时间:2022-09
期刊:The Anatomical Record
影响因子:--
作者:Liyuan Wang;Tianyang Yu;Feixue Dong;Jiayu Xu;Jin Fu;He Sun
通讯作者:Liyuan Wang;Tianyang Yu;Feixue Dong;Jiayu Xu;Jin Fu;He Sun
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