Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5

Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5
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DOI:
10.1007/s10571-006-9028-x
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发表时间:
2006-03-01
影响因子:
4
通讯作者:
Niwa, Masami
Niwa, Masami
中科院分区:
医学3区
文献类型:
--
作者:
Honda, Masaru;Nakagawa, Shinsuke;Niwa, Masami

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1.目的:脑血管内皮细胞分泌的肾上腺髓质素(Adrenomedullin,AM)具有多功能的生物学特性. AM影响脑血流量和血脑屏障(BBB)功能。我们研究了AM对脑微血管内皮细胞(BMEC)渗透性和紧密连接蛋白的作用。方法:分离大鼠BMEC,建立体外血脑屏障模型。通过测量跨内皮电阻(TEER)、荧光素钠和伊文思蓝白蛋白的通透性来研究屏障功能。采用免疫细胞化学和免疫印迹法检测细胞间紧密连接蛋白的表达.结果:AM呈剂量依赖性增加BMEC的TEER。免疫细胞化学结果显示,AM以剂量依赖性方式增强细胞接触部位的claudin-5表达。结论:AM通过过表达claudin-5抑制血脑屏障的细胞旁转运。
1. Aims: Brain vascular endothelial cells secret Adrenomedullin (AM) has multifunctional biological properties. AM affects cerebral blood flow and blood-brain barrier (BBB) function. We studied the role of AM on the permeability and tight junction proteins of brain microvascular endothelial cells (BMEC).2. Methods: BMEC were isolated from rats and a BBB in vitro model was generated. The barrier functions were studied by measuring the transendothelial electrical resistance (TEER) and the permeability of sodium fluorescein and Evans' blue albumin. The expressions of tight junction proteins were analyzed using immunocytochemistry and immunoblotting.3. Results: AM increased TEER of BMEC monolayer dose-dependently. Immunocytochemistry revealed that AM enhanced the claudin-5 expression at a cell-cell contact site in a dose-dependent manner. Immunoblotting also showed an overexpression of claudin-5 in AM exposure.4.Conclusions: AM therefore inhibits the paracellular transport in a BBB in vitro model through claudin-5 overexpression.