Digoxin immune fab protects endothelial cells from ouabain-induced barrier injury.
Digoxin immune fab protects endothelial cells from ouabain-induced barrier injury.
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DOI：
10.1111/j.1600-0897.2011.01055.x
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Adair CD
中科院分区：
文献类型：
--
作者：
Wang Y;Fan R;Gu Y;Adair CD
内源性地黄样因子（EDLF）抑制钠泵Na+ / K+ atp酶活性，母体EDLF水平在子痫前期（PE）升高。本研究确定地高辛免疫Fab （DIF）是否能保护内皮细胞（ECs）免受edlf诱导的内皮屏障功能障碍。在存在或不存在DIF的情况下，用递增剂量的乌阿拜（一种已知的EDLF）治疗ECs。通过连接蛋白VE-cadherin和occludin的表达检测EC屏障的完整性。采用辣根过氧化物酶（HRP）渗漏和经内皮电阻（TEER）测定EC通透性。瓦巴因处理后，细胞EC连接蛋白ve -钙粘蛋白分布被破坏。DIF不控制IgG Fab片段，但能阻断瓦他因诱导的VE-cadherin和occludin表达下降，阻止瓦他因诱导的HRP渗漏和TEER改变。DIF可保护内皮细胞免受瓦苦因诱导的屏障损伤，这为DIF对内皮细胞功能的有益作用提供了证据，并支持Na+ /K+ atp酶可能是改善内皮功能障碍的治疗靶点。
Endogenous digitalis-like factors (EDLF) inhibit sodium pump Na+ / K+ATPase activity, and maternal EDLF levels are elevated in preeclampsia (PE). This study determined whether digoxin immune Fab (DIF) could protect endothelial cells (ECs) from EDLF-induced endothelial barrier dysfunction. ECs were treated with escalating doses of ouabain (a known EDLF) in the presence or absence of DIF. EC barrier integrity was examined by junction protein VE-cadherin and occludin expressions. EC permeability was determined by horseradish-peroxidase (HRP) leakage and transendothelial electrical resistance (TEER). EC junction protein VE-cadherin distribution was disrupted in cells treated with ouabain. DIF, but not control IgG Fab fragment, blocked ouabain-induced decreases in VE-cadherin and occludin expressions and prevented ouabain-induced HRP leakage and TEER changes. DIF protects ECs from ouabain-induced barrier injury, providing evidence of beneficial effects of DIF on EC function and supporting that Na+ /K+ATPase might be a therapeutic target to ameliorate endothelial dysfunction.