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Colloidal gold particles as a new in vivo marker of early acute lung injury.

机译:胶体金颗粒作为早期急性肺损伤的新体内标志物。

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Permeability of the endothelial barrier to large molecules plays a pivotal role in the manifestation of early acute lung injury. We present a novel and sensitive technique that brings microanatomical visualization and quantification of microvascular permeability in line. White New Zealand rabbits were anesthetized and ventilated mechanically. Rabbit serum albumin (RSA) was labeled with colloidal gold particles. We quantified macromolecular leakage of gold-labeled RSA and thickening of the gas exchange distance by electron microscopy, taking into account morphology of microvessels. The control group receiving a saline solution represented a normal gas exchange barrier without extravasation of gold-labeled albumin. Infusion of lipopolysaccharide (LPS) resulted in a significant displacement of gold-labeled albumin into pulmonary cells, the lung interstitium, and even the alveolar space. Correspondingly, intravital fluorescence microscopy and digital image analysis indicated thickening of width of alveolarsepta. The findings were accompanied by a deterioration of alveolo-arterial oxygen difference, whereas wet/dry ratio and albumin concentration in the bronchoalveolar lavage fluid failed to detect that early stage of pulmonary edema. Inhibition of the nuclear enzyme poly(ADP-ribose) synthetase by 3-aminobenzamide prevented LPS-induced microvascular injury. To summarize: colloidal gold particles visualized by standard electron microscopy are a new and very sensitive in vivo marker of microvascular permeability in early acute lung injury. This technique enabling detailed microanatomical and quantitative pathophysiological characterization of edema formation can form the basis for evaluating novel treatment strategies against acute lung injury.
机译:内皮屏障对大分子的渗透性在早期急性肺损伤的表现中起关键作用。我们提出了一种新颖而灵敏的技术,可带来微解剖学的可视化和微血管通透性的定量分析。将新西兰白兔麻醉并进行机械通气。兔血清白蛋白(RSA)用胶体金颗粒标记。考虑到微血管的形态,我们通过电子显微镜定量了金标记的RSA的大分子泄漏和气体交换距离的增加。接受盐溶液的对照组代表正常的气体交换屏障,没有渗出金标记的白蛋白。注入脂多糖(LPS)导致金标记的白蛋白大量置换进入肺细胞,肺间质甚至肺泡腔。相应地,活体荧光显微镜检查和数字图像分析表明肺泡变宽。这些发现伴随着肺泡-动脉氧差的恶化,而支气管肺泡灌洗液中的干/湿比和白蛋白浓度未能检测到早期的肺水肿。 3-氨基苯甲酰胺对核酶聚(ADP-核糖)合成酶的抑制作用可防止LPS诱导的微血管损伤。总结:通过标准电子显微镜观察的胶体金颗粒是早期急性肺损伤中微血管通透性的一种新的且非常敏感的体内标记。这项技术可对水肿形成进行详细的微观解剖学和定量病理生理学表征,可为评估针对急性肺损伤的新型治疗策略奠定基础。

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