Jang An-Soo, Lee Jong-Un, Choi Inseon-S, Park Kyung-Ok, Lee June Hyuk, Park Sung-Woo, Park Choon-Sik
Department of Internal Medicine, Soonchunhyang University Hospital, 1174 Jung-dong, Wonmi-gu, Bucheon-si, 420-767 Gyeonggi-do, Republic of Korea.
Intensive Care Med. 2004 Mar;30(3):489-95. doi: 10.1007/s00134-003-2129-9. Epub 2004 Feb 6.
Nitric oxide (NO) and aquaporins (AQPs) are believed to play an important role in the pathogenesis of pulmonary inflammation and edema. The aim of this study was to investigate the role of NO synthase (NOS) and AQP in acute lung injury (ALI) lung following bleomycin inhalation in rats.
A prospective controlled trial in a university research laboratory.
Sprague-Dawley rats were treated by inhalation of 10 U/kg bleomycin hydrochloride in 5 ml of normal saline. Control rats were treated with 5 ml normal saline alone. The animals (6-8 rats per group) were killed on days 4, 7 or 14.
We analyzed the change in expression of inducible NOS (iNOS), neuronal NOS (nNOS), endothelial NOS (eNOS), aquaporin 1 (AQP1) and aquaporin 5 (AQP5) over time by Western blot. Nitrate and nitrite concentrations were measured in bronchoalveolar lavage fluid (BALF) using a modified Griess reaction. The nitrite and nitrate concentrations in BALF from rats 4 days after bleomycin exposure were greater than those from saline-treated rats. Immunoblotting studies demonstrated increased levels of eNOS in the rat lung at 4, 7 and 14 days and iNOS at 7 and 14 days after bleomycin inhalation. However, nNOS expression was unaltered. Although AQP1 expression was decreased in rats at 4 days, AQP5 expression was increased at 4, 7 and 14 days.
This study demonstrates that NO metabolites increase along with eNOS and iNOS expression during the acute exudative phase in ALI, and that AQP and NOS are regulated independently in bleomycin-induced pulmonary edema.
一氧化氮（NO）和水通道蛋白（AQPs）被认为在肺部炎症和水肿的发病机制中起重要作用。本研究旨在探讨一氧化氮合酶（NOS）和水通道蛋白在博来霉素吸入诱导的大鼠急性肺损伤（ALI）肺中的作用。
在大学研究实验室进行的前瞻性对照试验。
将Sprague-Dawley大鼠通过吸入5ml生理盐水中的10U/kg盐酸博来霉素进行处理。对照大鼠仅用5ml生理盐水处理。在第4、7或14天处死动物（每组6-8只大鼠）。
我们通过蛋白质印迹法分析诱导型NOS（iNOS）、神经元型NOS（nNOS）、内皮型NOS（eNOS）、水通道蛋白1（AQP1）和水通道蛋白5（AQP5）表达随时间的变化。使用改良的格里斯反应测量支气管肺泡灌洗液（BALF）中的硝酸盐和亚硝酸盐浓度。博来霉素暴露后4天大鼠BALF中的亚硝酸盐和硝酸盐浓度高于生理盐水处理的大鼠。免疫印迹研究表明，博来霉素吸入后第4、7和14天大鼠肺中eNOS水平升高，第7和14天iNOS水平升高。然而，nNOS表达未改变。虽然第4天大鼠中AQP1表达降低，但第4、7和14天AQP5表达增加。
本研究表明，在ALI的急性渗出期，NO代谢产物随eNOS和iNOS表达增加，并且在博来霉素诱导的肺水肿中AQP和NOS是独立调节的。
