Time Course for Expression of VEGF and Its Receptor and Regulator Levels of Contraction and Relaxation in Increased Vascular Permeability of Lung Induced by Phosgene
Time Course for Expression of VEGF and Its Receptor and Regulator Levels of Contraction and Relaxation in Increased Vascular Permeability of Lung Induced by Phosgene
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DOI：
10.1080/08958370802015091
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发表时间：
2008-01
影响因子：
2.1
通讯作者：
Xiao-di Zhang;C. Hai;Feng-lei Cai;Xin Liang;R. Liu;Hong-li Chen;X. Qin;An-ji Feng
中科院分区：
文献类型：
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作者：
Xiao-di Zhang;C. Hai;Feng-lei Cai;Xin Liang;R. Liu;Hong-li Chen;X. Qin;An-ji Feng
光气引起的急性肺损伤(ALI)增加了严重浮肿和死亡的风险。微血管内皮细胞通透性增加与ALI的进展有关，但渗出过程中血管调节因子的加工相互作用和时程活性仍不清楚。本研究的主要目的是探讨血管内皮生长因子(VEGF)及其受体和一些血管功能调节因子在光气肺血管通透性增加中的时程变化及可能的作用。SD大鼠按光气暴露后时间随机分为7组(对照组、1、3、6、12、24、48h组)。采用逆转录-聚合酶链式反应(RT-PCR)和酶联免疫吸附试验(ELISA)检测肺组织中血管内皮生长因子(VEGF)亚型、FMS样酪氨酸激酶受体1(Flt-1)和KDR/Flk-1的表达。采血检测血浆内皮素-1(ET-1)和一氧化氮(NO)水平。结果表明，光气暴露后，血管内皮生长因子系统的mRNA和蛋白表达谱具有时间依赖性。肺组织中血管内皮生长因子系统的表达与ET-1、NO水平密切相关。综上所述，光气致肺微血管内皮细胞通透性增加主要是由于血管内皮生长因子及其受体表达差异所致，并与ET-1和NO水平有关。结果表明，血管内皮生长因子系统、ET-1和NO的协同作用在光气诱导的血管通透性过程中起着重要作用，并且这些参数在光气诱导的渗透过程的早期阶段呈时间依赖性。
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.