COMP-Angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury
COMP-Angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury
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DOI：
10.1038/ki.2009.387
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发表时间：
2009-12-01
影响因子：
19.6
通讯作者：
Kim, Won
中科院分区：
文献类型：
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作者：
Kim, Duk Hoon;Jung, Yu Jin;Kim, Won
脓毒症期间内皮功能障碍是急性肾损伤（AKI）的重要发病机制。脂多糖（LPS）诱导的内毒素血症与肾血流动力学变化有关，例如肾血流量（RBF）、血管阻力和肾小球滤过率的改变。我们使用腺病毒递送具有抗炎和抗渗透功能的天然血管生成素-1 (COMP-angiopoietin-1) 的工程变体，以确定肾内皮细胞功能障碍的调节是否可能在小鼠 LPS 诱导的内毒素血症期间预防 AKI 中发挥有益作用。这种治疗可防止内毒素引起的 RBF 和平均动脉压下降，同时提高肾小球滤过率。治疗还减轻了LPS对肾细胞间粘附分子-1和血管细胞粘附分子-1蛋白表达、浸润肾脏的ER-HR3阳性巨噬细胞数量、血清硝酸盐/亚硝酸盐水平、肾诱导型一氧化氮合酶蛋白表达、肾小管上皮活性氧和氮物种的诱导以及肾微血管通透性的影响。我们的研究结果表明，COMP-angiopoietin-1（一种内皮导向治疗剂）可预防内毒素血症引起的 AKI。肾脏国际 (2009) 76, 1180-1191; doi：10.1038/ki.2009.387； 2009 年 10 月 7 日在线发布
During sepsis endothelial dysfunction is an important pathogenetic mechanism in acute kidney injury (AKI). Lipopolysaccharide (LPS)-induced endotoxemia is associated with renal hemodynamic changes such as alterations of renal blood flow (RBF), vascular resistance, and glomerular filtration rate. We used adenoviral delivery of an engineered variant of native angiopoietin-1 (COMP-angiopoietin-1) containing anti-inflammatory and anti-permeability functions, to determine if regulation of renal endothelial cell dysfunction may have a beneficial role in preventing AKI during LPS-induced endotoxemia in mice. This treatment prevented the endotoxin-induced decrease of RBF and mean arterial pressure while improving glomerular filtration rate. Treatment also mitigated the effects of LPS on renal intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 protein expression, the number of ER-HR3-positive macrophages that infiltrated the kidney, serum nitrate/nitrite levels, renal inducible nitric oxide synthase protein expression, the induction of tubular epithelial reactive oxygen and nitrogen species, and renal microvascular permeability. Our findings show that COMP-angiopoietin-1, an endothelium-oriented therapeutic agent, protects against AKI caused by endotoxemia. Kidney International (2009) 76, 1180-1191; doi:10.1038/ki.2009.387; published online 7 October 2009