首页> 外文期刊>American Journal of Physiology >Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells.
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Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells.

机译:缺血性急性肾衰竭中的内皮功能障碍:通过移植的内皮细胞进行抢救。

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摘要

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.
机译:有越来越多的环境证据表明,内皮细胞功能障碍是缺血性肾脏中“无回流”现象的原因。在这里,我们证明了体外,离体和体内内皮细胞暴露于病理生理相关损伤(例如氧化应激和亚硝化应激或缺血)的脆弱性。所有这些刺激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,这提供了不回流现象的存在的直接证据,该现象至少部分归因于内皮损伤。为了改善失去的内皮完整性所造成的血液动力学后果,我们将表达内皮型一氧化氮合酶的内皮细胞或替代细胞移植到了接受肾动脉钳制的大鼠中。在肾微脉管系统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可对缺血性肾脏起到显着的功能性保护作用。这些观察结果强烈提示内皮细胞功能障碍是无回流现象的主要原因,当这种现象得到改善时,可以预防急性肾衰竭中出现的肾脏损伤。

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