Circ Res:赖仞组揭示缺铁性贫血和口服避孕药诱导脑卒中分子机制

2020-08-17 BioArt

缺血性脑卒中通常是由血管阻塞引起的,约占中风的87%。简而言之,缺血性脑卒中是在血管阻塞引起的脑血流严重减少或中断后发生的。当前,缺血性脑卒中是全球第二大死因,也是永久性残疾的最重要原因。

缺血性脑卒中通常是由血管阻塞引起的,约占中风的87%。简而言之,缺血性脑卒中是在血管阻塞引起的脑血流严重减少或中断后发生的。当前,缺血性脑卒中是全球第二大死因,也是永久性残疾的最重要原因。两种诱栓因素,包括缺铁性贫血和联合口服避孕药的使用均与脑卒中的患病风险增加相关,但其潜在分子机制尚不确定。缺铁性贫血是全球最常见的营养失调症,在全球范围内影响着超过约20亿人口。早在三十年前就发现缺铁性贫血与偏瘫和失语症相关。而在过去的几年中,缺铁性贫血与血栓栓塞疾病,例如,视网膜中央静脉阻塞、脑静脉窦血栓形成和颈动脉血栓形成等之间的联系已得到越来越多的认识。同样的,大量研究也表明使用口服避孕药的女性患脑卒中的风险显着增加,是造成育龄期女性脑卒中的危险因素之一。

近日,中国科学院昆明动物研究所赖仞研究员领导的团队在Circulation Research杂志上发表文章Iron-Deficiency and Estrogen Are Associated with Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability,发现缺铁和雌激素分别通过调控转铁蛋白基因调控区的低氧诱导元件(HRE)和雌激素反应元件(ERE)从而上调转铁蛋白的表达,这表明转铁蛋白上调与缺铁性贫血和口服避孕药的使用之间存在关联(该文章被遴选为第5期的封面文章)。

前期研究已经阐明血浆转铁蛋白与凝血因子和抗凝血因子以不同的亲和力相互作用以维持凝血系统稳态平衡。进一步的小鼠模型实验发现外源性转铁蛋白处理、缺铁性贫血、雌激素给药或转铁蛋白过表达可以诱导高凝倾向和缺血性脑卒中的发病,而转铁蛋白抗体干预、转铁蛋白敲降和设计的干预多肽则能显着的减轻脑卒中的发病。这些数据表明,上调的转铁蛋白是脑卒中发病的危险因素并且是与铁缺性贫血和口服避孕药诱导血栓形成相关的重要关联因子。该研究也进一步证实了转铁蛋白在维持凝血系统稳态平衡中的核心作用。该研究为与缺铁性贫血和口服避孕药相关的血栓疾病的药物开发提供了全新的途径和思路。

该论文的第一作者为唐小芃副研究员;昆明动物研究所的方鸣谦博士研究生、程若梅博士研究生、张治业副研究员和申传斌助理研究员以及昆明医科大学第二附属医院检验科的王玉明主任为该论文的共同第一作者;赖仞研究员为该论文的唯一通讯作者。

原始出处:

Xiaopeng Tang, Mingqian Fang, Ruomei Cheng, et al.Iron-Deficiency and Estrogen Are Associated With Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability.Circ Res. 2020 Aug 14;127(5):651-663. doi: 10.1161/CIRCRESAHA.119.316453. Epub 2020 May 26.

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    2020-08-19 ms5000000741733160

    👍🏻

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    2020-08-17 健健

    卒中虽然是临床上常见病,溶栓,取栓等血管内治疗也很成熟,但是仍然有很多未知问题有待认知!

    0

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    2020-08-17 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

    0

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