Zhang Xiao-di, Hai Chun-Xu, Cai Feng-Lei, Liang Xin, Liu Rui, Chen Hong-Li, Qin Xu-Jun, Feng An-Ji
Department of Toxicology, The Fourth Military Medical University, Xi'an, People's Republic of China.
Inhal Toxicol. 2008 Jul;20(9):805-12. doi: 10.1080/08958370802015091.
Acute lung injury (ALI) induced by phosgene increases risk of serious edema and mortality. Increased permeability of the microvascular endothelium is implicated in the progression of ALI, but the processing interaction and time course activity of the vascular regulators in exudation are still not understood. The main aim of this study was to investigate the time course and potential role for vascular endothelial growth factor (VEGF), its receptors, and some vascular function regulators related to increased vascular permeability of lung induced by phosgene. Sprague Dawley rats were randomly divided into seven groups according to time post phosgene exposure (control, and 1, 3, 6, 12, 24, and 48 h groups). Lung tissue was removed to evaluate VEGF isoforms, fms-like tyrosine kinase receptor 1 (Flt-1), and kinase insert domain containing region (KDR/Flk-1) by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for measurement of plasma endothelin-1 (ET-1) and nitric oxide (NO) level. The results showed that the mRNA and protein expression profile of the VEGF system after phosgene exposure was time dependent. The VEGF system expression in lung tissue was related closely to the level of ET-1 and NO. In conclusion, increased permeability of the lung microvascular endothelium induced by phosgene was primarily a result of differential expression of VEGF and its receptors, and was related to the level of ET-1 and NO. The results suggest that the cooperation of VEGF system, ET-1, and NO plays a critical role, and all those parameters emerge as time dependent in the early phase of the permeability process induced by phosgene exposure.
光气诱导的急性肺损伤（ALI）会增加严重水肿和死亡风险。微血管内皮通透性增加与ALI的进展有关，但血管调节因子在渗出过程中的相互作用及时间进程活性仍不清楚。本研究的主要目的是探讨血管内皮生长因子（VEGF）及其受体，以及一些与光气诱导的肺血管通透性增加相关的血管功能调节因子的时间进程及潜在作用。将Sprague Dawley大鼠根据光气暴露后的时间随机分为七组（对照组、1小时、3小时、6小时、12小时、24小时和48小时组）。取出肺组织，通过逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）评估VEGF异构体、fms样酪氨酸激酶受体1（Flt-1）和含激酶插入结构域区域（KDR/Flk-1）。采集血样以测定血浆内皮素-1（ET-1）和一氧化氮（NO）水平。结果表明，光气暴露后VEGF系统的mRNA和蛋白表达谱呈时间依赖性。肺组织中VEGF系统的表达与ET-1和NO水平密切相关。总之，光气诱导的肺微血管内皮通透性增加主要是VEGF及其受体差异表达的结果，且与ET-1和NO水平有关。结果表明，VEGF系统、ET-1和NO的协同作用起关键作用，并且在光气暴露诱导的通透性过程早期，所有这些参数均呈时间依赖性出现。
