Colloidal gold particles as a new in vivo marker of early acute lung injury
Colloidal gold particles as a new in vivo marker of early acute lung injury
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DOI：
10.1152/ajplung.00078.2004
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发表时间：
2004-10-01
影响因子：
4.9
通讯作者：
Goetz, AE
中科院分区：
文献类型：
--
作者：
Heckel, K;Kiefmann, R;Goetz, AE
内皮屏障对大分子的通透性在早期急性肺损伤的表现中起着关键作用。我们提出了一种新的和敏感的技术，使显微解剖可视化和微血管通透性的定量线。将白色新西兰兔麻醉并机械通气。用胶体金标记兔血清白蛋白。我们定量的金标记RSA的大分子泄漏和增厚的气体交换距离的电子显微镜，考虑到微血管的形态。接受生理盐水的对照组代表正常的气体交换屏障，没有金标记白蛋白外渗。脂多糖（LPS）的输注导致金标白蛋白进入肺细胞，肺小叶，甚至肺泡腔的显着位移。相应地，活体荧光显微镜和数字图像分析表明肺泡间隔的宽度增厚。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湿/干比和白蛋白浓度未能检测到早期肺水肿。3-氨基苯甲酰胺抑制核酶聚（ADP-核糖）合成酶可防止LPS诱导的微血管损伤。总结一下：通过标准电子显微镜观察到的胶体金颗粒是早期急性肺损伤中微血管通透性的新的和非常敏感的体内标记物。这种技术能够详细的微观解剖和定量的病理生理学特征的水肿形成，可以形成的基础上，评估新的治疗策略，对急性肺损伤。
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 alveolar septa. 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.