Angiopoietin-1 increases survival and reduces the development of lung edema induced by endotoxin administration in a murine model of acute lung injury
Angiopoietin-1 increases survival and reduces the development of lung edema induced by endotoxin administration in a murine model of acute lung injury
复制标题
DOI：
10.1097/01.ccm.0000297955.02633.a4
复制
发表时间：
2008-01-01
影响因子：
8.8
通讯作者：
Hay, John G.
中科院分区：
文献类型：
--
作者：
Huang, Yao Qi;Sauthoff, Harald;Hay, John G.
目的：评价血管生成素-1（一种血管生成生长因子）对急性肺损伤小鼠模型肺毛细血管渗漏和存活的影响。设计：实验室研究。纽约大学医学院和退伍军人事务部的研究实验室，纽约港医疗保健系统。受试者：C57 BL/6小鼠，体重18-20 g，易受内毒素诱导的急性肺损伤。干预：通过腹腔内注射内毒素在C57 BU 6小鼠中诱导急性肺损伤。血管生成素-1，从一个非复制型E1 a缺失腺病毒含有血管生成素-1互补DNA（AdAng 1）表达，对生存和肺损伤的影响进行了评价。使用不含转基因的E1 a缺失腺病毒（Ad 312）和磷酸盐缓冲盐水作为对照。免疫印迹法检测到血管生成素-1蛋白在小鼠的血清中接受腹腔注射的AdAng 1，但没有在小鼠接受对照病毒Ad 312。与对照组相比，在内毒素给药前5天接受AdAng 1的小鼠存活率提高，从循环到肺部的蛋白质渗漏显著减少，这通过伊文思蓝染料的定量分光光度测量来检测。此外，与对照组相比，组织病理学和肺对CD 31和平滑肌肌动蛋白的免疫染色表明，在用AdAng 1预处理的小鼠中，血管完整性得到保护，组织损伤减少。当内毒素给药前感染AdAng 1的3小时，没有效益observed.Conclusions：这些数据表明，腺病毒介导的血管生成素-1的表达可以保护对肺毛细血管蛋白渗漏的发展，降低内毒素诱导的死亡率。然而，与肺损伤发生相关的AdAng 1给药时机可能至关重要。
Objective: To evaluate the effect of angiopoietin-1, an angiogenic growth factor, on lung capillary leakage and survival in a murine model of acute lung injury.Design: Laboratory investigation.Setting. Research laboratory at New York University School of Medicine and Department of Veterans Affairs, NY Harbor Healthcare System.Subjects: C57BL/6 mice weighing 18-20 g, susceptible to endotoxin-induced acute lung injury.Interventions: Acute lung injury was induced in C57BU6 mice by the intraperitoneal administration of endotoxin. The effects of angiopoietin-1, expressed from a nonreplicating E1a-deleted adenovirus containing the angiopoietin-1 complementary DNA (AdAng1), on survival and lung injury were evaluated. An E1a-deleted adenovirus that does not contain a transgene (Ad312) and phosphate-buffered saline were used as controls.Measurements and Main Results. Angiopoietin-1 protein was detected by immunoblotting in the serum of mice that received an intraperitoneal injection of AdAng1 but not in mice that received the control virus Ad312. When compared with control groups, mice that received AdAng1 5 days before endotoxin administration had improved survival and significantly less protein leakage from the circulation into the lungs, as detected by quantitative spectrophotometric measurements of Evans blue dye. Furthermore, when compared with controls, histopathology and immunostaining of lungs against CD31 and smooth muscle actin suggested preservation of vascular integrity and decreased tissue damage in mice pretreated with AdAng1. When endotoxin administration preceded infection with AdAng1 by 3 hrs, no benefit was observed.Conclusions: These data show that adenoviral mediated expression of angiopoietin-1 can protect against the development of lung capillary protein leak and decrease the mortality induced by endotoxin. However, the timing of AdAng1 administration in relation to the onset of lung injury may be critical.