Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells
Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells
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DOI：
10.1152/ajprenal.00329.2001
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发表时间：
2002-06-01
影响因子：
4.2
通讯作者：
Goligorsky, MS
中科院分区：
文献类型：
--
作者：
Brodsky, SV;Yamamoto, T;Goligorsky, MS
有越来越多的间接证据表明，内皮细胞功能障碍有助于缺血后肾脏的“无复流”现象。在这里，我们证明了在体外，离体和体内内皮细胞暴露于病理生理相关的侮辱，如氧化和亚硝化应激或缺血的脆弱性。所有这些刺激都损害了内皮衬里的完整性。接下来，我们对肾小管周围毛细血管的血流进行了微创活体显微镜检查，这提供了无复流现象存在的直接证据，至少部分归因于内皮损伤。在试图改善血流动力学后果失去内皮完整性，我们移植内皮细胞或替代细胞表达内皮型一氧化氮合酶到大鼠肾动脉钳夹。在肾微血管中植入表达功能性内皮型一氧化氮合酶的内皮细胞或其替代物导致缺血肾的显著功能保护。这些观察结果强烈表明，内皮细胞功能障碍是无复流现象的主要原因，当改善时，可预防急性肾衰竭中出现的肾损伤。
There is accumulating circumstantial evidence suggesting that endothelial cell dysfunction contributes to the "no-reflow" phenomenon in postischemic kidneys. Here, we demonstrated the vulnerability of in vitro, ex vivo, and in vivo endothelial cells exposed to pathophysiologically relevant insults, such as oxidative and nitrosative stress or ischemia. All of these stimuli compromised the integrity of the endothelial lining. Next, we performed minimally invasive intravital microscopy of blood flow in peritubular capillaries, which provided direct evidence of the existence of the no-reflow phenomenon, attributable, at least in part, to endothelial injury. In an attempt to ameliorate the hemodynamic consequences of lost endothelial integrity, we transplanted endothelial cells or surrogate cells expressing endothelial nitric oxide synthase into rats subjected to renal artery clamping. Implantation of endothelial cells or their surrogates expressing functional endothelial nitric oxide synthase in the renal microvasculature resulted in a dramatic functional protection of ischemic kidneys. These observations strongly suggest that endothelial cell dysfunction is the primary cause of the no-reflow phenomenon, which, when ameliorated, results in prevention of renal injury seen in acute renal failure.