权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pathogenesis and Therapy for Ventilator-Induced Lung Injury (VILI)

呼吸机引起的肺损伤 (VILI) 的发病机制和治疗

基本信息

批准号：
15591629
负责人：
NISHINA Kahoru
金额：
$ 1.79万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Ventilation is known to cause acute lung injury (ALI) in animals and often worsens lung damages in human ALI (ventilator-induced lung injury [VILI]). Many inflammatory cytokines released from alveolar epithelial type II cells (AEC-II) and apoptosis of AEC-II are thought to play an important role in the pathogenesis of VILI. We first investigated the effects of mechanical stretch on production of chemokine from AEC-II. Mechanical stress on rat cultured AEC-II per se did not stimulate release of GRO/CINC-1 but increased endotoxin-induced production of GRO/CINC-1. Secondly, we examined the effects of hypercapnic acidosis on chemokine production from AEC-II and apoptosis of the pneumocytes. Hypercapnia in the culture medium (PCO2 : 70-80mmHg) stimulated A549 cells, human AEC-II, IL-8 production as assessed by ELISA. IL-8 production was increased by inducing mRNA expression. Hypercapnic acidosis also multiplied endotoxin-induced IL-8 production. These data suggest that hypercapnic acidosis up-regulates inflammatory cytokines at the transcriptional level. Finally, we evaluated whether hypercapnia can change apoptosis of AEC-II. Hypercapnic acidosis per se slightly induced apoptosis of A549 cells (as assessed by APOPercentage Apoptosis Kit) although not significantly. Hypercapnic acidosis had no effect on apoptosis of A549 cells induced by hydrogen peroxide. These findings suggest that low tidal ventilation does not induce or potentiate apoptosis of AEC-II

已知通气可导致动物急性肺损伤（ALI），并经常导致人ALI的肺损伤（通气机诱导的肺损伤[VILI]）。肺泡Ⅱ型上皮细胞（AEC-II）释放的多种炎性细胞因子和AEC-II的凋亡被认为在VILI的发病机制中起重要作用。我们首先研究了机械拉伸对AEC-II产生趋化因子的影响。机械应力对大鼠培养的AEC-II本身没有刺激释放GRO/CINC-1，但增加内毒素诱导的GRO/CINC-1的生产。其次，我们研究了高碳酸酸中毒对AEC-Ⅱ产生趋化因子和肺细胞凋亡的影响。培养液中的高碳酸血症（PCO 2：70- 80 mmHg）刺激A549细胞，通过ELISA评估人AEC-II、IL-8的产生。通过诱导mRNA表达增加IL-8的产生。高碳酸酸中毒也增加了内毒素诱导的IL-8的产生。这些数据表明，高碳酸酸中毒上调炎症细胞因子在转录水平。最后，我们评估了高碳酸血症是否可以改变AEC-II的凋亡。高碳酸酸中毒本身轻微诱导A549细胞凋亡（通过APOPercentage Apoptosis Kit评估），但不显著。高碳酸酸中毒对过氧化氢诱导的A549细胞凋亡无影响。这些结果表明，低潮通气不会诱导或加强AEC-Ⅱ的凋亡