Gene therapy for acute lung injury

急性肺损伤的基因治疗

基本信息

批准号：
08671508
负责人：
IZUMI Keiichi
金额：
$ 1.41万
依托单位：
Akita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

It has been reported that reperfusion is the most important factor in ischemia-reperfusion injury. However, causes of ischemia-reperfusion injury in the lung are controversial, because oxygen is always supplied if ventilation continues. Therefore, we hypothesized that nonhypoxic ischemia without reperfusion is sufficient for lung injury. To test our hypothesis, we measured both hydrogen peroxide (H_2O_2)production in the pulmonary circulation by digital imaging fluorescent dichlorofluorescein and the microvascular permeability (MVP) by the Evans blue extravasation technique in the nonhypoxic ischemia rat lung. We made a nonhypoxic ischemia rat lung by clamping the left pulmonary artery. Both H_2O_2 production and MVP increased in the nonhypoxic ischemia rat lung. We also determined the effect of oxygen removal by clamping bronchus in advance of pulmonary artery occlusion, intercellular adhesion molecule-1 (ICAM-1) neutralization with monoclonal antibody 1A29, and plateletactivating factor (PAF) receptor antagonist CV6209 on H_2O_2 production and MVP.These treatmrnts inhibited both H_2O_2 production and MVP increase. At high power viewing of the fluorescent dichlorofluorescein image, H_2O_2 was detected in the leukocytes within pulmonary capillaries. These data indicate that the nonhypoxic ischemia without reperfusion alone causes radical production and increases MVP.Furthermore, PAF and ICAM-1 contribute to these reactions.

据报道，再灌注是缺血再灌注损伤中最重要的因素。然而，肺部缺血 - 重新灌注损伤的原因是有争议的，因为如果继续通风，总是会提供氧气。因此，我们假设没有再灌注的非氧化缺血足以容纳肺损伤。为了检验我们的假设，我们通过数字成像荧光二氯荧光素和微血管渗透性（MVP）在肺部循环中测量了过氧化氢（H_2O_2）的产生。我们通过夹紧左肺动脉来制作非高毒性缺血大鼠肺。在非毒性缺血大鼠肺中，H_2O_2的产生和MVP增加。我们还通过在肺动脉抑制之前夹紧支气管，细胞间粘附分子1（ICAM-1）用单克隆抗体1A29中和血小板激活因子（PAF）受体抗体CV620在H_2O_2的生产和MVP PRING的HH_2O.2O.2O.2 MVP增加。在荧光二氯荧光素图像的高功率观察处，在肺毛细血管内的白细胞中检测到H_2O_2。这些数据表明，单独再灌注的非毒性缺血会导致根本性产生，并增加MVP。Furthermore，PAF和ICAM-1会导致这些反应。