Uchida Tokujiro, Shirasawa Madoka, Ware Lorraine B, Kojima Katsuo, Hata Yutaka, Makita Koshi, Mednick Gabe, Matthay Zachary A, Matthay Michael A
Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Am J Respir Crit Care Med. 2006 May 1;173(9):1008-15. doi: 10.1164/rccm.200509-1477OC. Epub 2006 Feb 2.
Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung.
To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury.
Rats were instilled intratracheally with 10 mg/kg lipopolysaccharide or hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL) and serum in the rats and in the pulmonary edema fluid and plasma from patients with acute lung injury (ALI; n = 22) and hydrostatic pulmonary edema (n = 11).
In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized approximately 48 kD. The elevated levels of RAGE in the BAL correlated well with the severity of experimentally induced lung injury. In the human studies, the RAGE level in the pulmonary edema fluid was significantly higher than the plasma level (p < 0.0001). The median edema fluid/plasma ratio of RAGE levels was 105 (interquartile range, 55-243). The RAGE levels in the pulmonary edema fluid from patients with ALI were higher than the levels from patients with hydrostatic pulmonary edema (p < 0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p < 0.001) or patients with hydrostatic pulmonary edema (p < 0.05).
RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.
晚期糖基化终末产物受体（RAGE）是肺中与I型肺泡细胞相关的蛋白之一。
检验RAGE是I型肺泡上皮细胞损伤标志物这一假说。
给大鼠气管内注入10 mg/kg脂多糖或盐酸。检测大鼠支气管肺泡灌洗（BAL）液和血清以及急性肺损伤（ALI；n = 22）和静水压性肺水肿（n = 11）患者的肺水肿液和血浆中的RAGE水平。
在大鼠肺损伤研究中，RAGE以单一大小约为48 kD的可溶性异构体形式释放到BAL液和血清中。BAL液中RAGE水平升高与实验性诱导的肺损伤严重程度密切相关。在人体研究中，肺水肿液中的RAGE水平显著高于血浆水平（p < 0.0001）。RAGE水平的水肿液/血浆中位数比值为105（四分位间距，55 - 243）。ALI患者肺水肿液中的RAGE水平高于静水压性肺水肿患者（p < 0.05），ALI患者的血浆RAGE水平显著高于健康志愿者（p < 0.001）或静水压性肺水肿患者（p < 0.05）。
基于对大鼠和ALI患者的实验研究，RAGE是I型肺泡上皮细胞损伤的标志物。
