Nature:内皮细胞TLR4和微生物导致脑海绵状血管畸形

2017-05-15 zhangfan MedSci原创

研究确定了海绵状血管畸形--这种脑血管病发病机制中微生物和先天免疫信号之间的微妙关系,将有助于人类对疾病的认识寻找治疗手段

海绵状血管畸形(CCMs)可引起中风和癫痫发作,目前尚无有效的治疗药物。CCMs的原因是配置器复合物功能失调导致大脑内皮细胞MEKK3-KLF2 / 4信号负向调节,但该疾病途径的上游激活因素尚未确定。

近日研究人员发现内皮细胞Toll样受体4 (TLR4)以及肠道菌群是CCM形成的关键兴奋因子。小鼠模型研究发现,革兰氏阴性细菌或脂多糖激活Toll样受体4可加速海绵状血管畸形的形成,遗传或药理学阻断TLR4信号可阻止小鼠CCM的形成。人类基因多态性研究发现,增加TLR4基因的表达或编码其共受体的基因CD14与海绵状血管畸形损伤相关。无菌小鼠对CCM免疫抗生素治疗可永久改变小鼠的CCM易感性。

该研究确定了海绵状血管畸形--这种脑血管病发病机制中微生物和先天免疫信号之间的微妙关系,将有助于人类对疾病的认识寻找治疗手段。

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    2017-08-28 liye789132251
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    2017-07-11 lilianxiang
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    2017-05-17 wushaoling
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    2017-05-17 cooco

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