胸部开放伤海水浸泡致急性肺损伤早期血管内皮生长因子水平变化

The Early Responses of VEGFs During Acute Lung Injury Induced by Immersion in Seawater after Open Chest Trauma

目的观察胸部开放伤海水浸泡致ALI早期血管内皮生长因子(VEGF)及其可溶性受体sVEGFR-1在血浆、BALF和肺组织的水平变化,探讨VEGF表达在胸部开放伤海水浸泡致ALI发病机制中的作用。方法16只成年杂交犬随机分为对照组(单纯胸部开放伤)和海水组(胸部开放伤海水浸泡致ALI)。于胸部开放伤后0、2、4、6及8 h,监测生命体征并取动、静脉血。测定各时相点外周血白细胞计数(WBC)、血气、电解质和血浆渗透压,采用ELISA法检测血浆IL-1β和IL-8水平,血管性血友病因子(vWF)水平,VEGF及受体sVEGFR-1水平。8 h取BALF和肺组织,HE染色观察肺组织病理改变,ELISA法检测BALF及肺组织匀浆中VEGF及受体sVEGFR-1水平。测定伤后8 hBALF和血浆中蛋白含量,并计算肺泡通透指数(BALF中蛋白含量/血浆蛋白含量)。结果与对照组比较,海水组肺组织病理切片见毛细血管扩张淤血严重,肺间质和肺泡腔内有大量水肿液积聚,部分肺泡结构的完整性破坏,肺泡融合。海水组BALF中蛋白渗出增加,肺泡通透指数(PPI)显著增加。外周血WBC、血浆渗透压、Na+、Cl-、IL-1β、IL-8和vWF水平均进行性升高。海水组伤后8 h血浆VEGF及sVEGFR-1表达明显增加,肺组织和BALF中的VEGF及sVEGFR-1表达明显减少。海水组血浆VEGF水平增加与炎性因子、渗透压增加呈正相关。结论胸部开放伤海水浸泡致ALI早期VEGF表达在血浆中明显升高,在肺组织和BALF中明显降低,血浆VEGF水平变化与海水高渗有明显相关性。

Objective To investigate the role of VEGF and its soluble VEGF receptor （sVEGFR-1） in pathogenesis of acute lung injury （ALI） induced by immersion in seawater after open chest trauma. Methods Sixteen hybridized adult dogs were randomly divided into control group and seawater group. The control group only suffered from open chest trauma, whereas the seawater group were exposed to seawater after open chest trauma. Blood samples were collected at the 0,2,4,6, 8 h after trauma for measurement of white blood cell count, arterial blood gas, plasma osmotic pressure （POP）, electrolyte concentration, IL-8, vWF, VEGF and sVEGFR-1 levels. The lungs tissue and BALF was collected at 8 h after trauma. Pathological changes of the lung was observed under light microscope by HE staining. Meanwhile VEGF and sVEGFR-1 levels were measured in BALF and lung tissue homogenate. Total protein concentrations in plasma and BALF were measured to calculate the pulmonary penetration index （PPI）. Results The lung of the seawater group showed interstitial mononuciear cell and neutrophil infiltration, interstitial edema, and vascular congestion. VEGF and sVEGFR-1 were significantly increased in the plasma, while VEGF was significantly reduced in the lung tissues and BALF. The levels of IL-1β,IL-8 and vWF,just as the level of VEGF, were significantly increased in the plasma. Meanwhile, the POP and electrolyte concentration were significantly increased. In the plasma, the responses of VEGFs during the early onset of ALI induced by immersion in seawater after open chest trauma were consistent with the POP and PPI. Conclusions High plasma levels and low BALF/lung tissue levels of VEGFs is a distinguishing characteristic during the early onset of ALI induced by immersion in seawater after open chest trauma. VEGF may be a novel biomarker which has an important role in the development of ALI.