EFFECTS OF MILD HYPOTHERMIA ON VENTILATOR LUNG INJURY AND RAT ACID-INDUCED ACUTE LUNG INJURY MODEL

轻度低温对呼吸机肺损伤及大鼠酸致急性肺损伤模型的影响

基本信息

批准号：
14571449
负责人：
NOGUCHI Takayuki
金额：
$ 2.18万
依托单位：
Oita University (2004)大分医科大学 (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Recent studies have clarified that mechanical stretching and pressure overload can induce lung injury and HSP70 in some tissues and cells. However, it remains unclear whether HSP70 is induced in stretch-subjected lungs, such as those under mechanical ventilation. The present study was designed to investigate the effects of high peak airway pressure(PAP) ventilation on HSP70 expression in intact rat lungs. Male Sprague-Dawley rats were randomly allocated to one of three groups : non-ventilated(anesthesia alone) control group(NVC) ; PAP 15 cmH_2O group(P15) ; and PAP 30 cmH_2O group(P30). Following the 30 min of pressure-controlled assisted ventilation, HSP70 expression in the P30 group was significantly upregulated in bronchiolar cells and subepithelial tissues at 12 h and this upregulation continued throughout the observation period. In contrast, there were no significant differences between the NVC and P15 groups, although HSP70 was upregulated in the P15 group at all time points. HSP … More 70 was induced by high PAP ventilation, but its specific role and induction mechanism remain unclear.Next he effects of mild hypothermia were studied on the expression of intercellular adhesion molecule-1(ICAM-1) and the accumulation of neutrophils after acid-induced lung injury in the rat. Oxygenation in acid-instilled rats was significantly impaired as compared to that in non-instilled groups, but induction of mild hypothermia gradually improved oxygenation. Expression of ICAM-1 was enhanced in the acid-instilled normothermic group. By contrast, no overexpression of ICAM-1 and its transcript was detected in the acid-instilled hypothermic group. In addition, accumulation of neutrophils was markedly inhibited after exposure to mild hypothermia irrespective of the instillation of acid. Our data suggest that mild hypothermia can inhibit the adhesion, activation, and accumulation of neutrophils in the acute phase of acid-induced lung injury and suggest an approach that might potentially reduce ongoing damage in patients with ARDS.Finally we studied effects of human urinary trypsin Inhibitor(Urinastatin UTI) on acid-induced lung injury. UTI is known to inhibit production of tumor necrosis factor(TNF)-a, which potently stimulates leukocyte activation. The purpose of this study was to clarify whether UTI improves acid-induced lung injury in rats by inhibiting activated leukocytes via TNF-aproduction. UTI significantly improved the OA-induced histological changes for 4 h after OA administration. The OA-induced reduction of PaO2, the increase of pulmonary vascular permeability, and the levels of MPO activity and TNF-a in lung tissues weresignificantly improved in rats administrated UTI. The effects in the leukocytopenia group were similar to those in the UTI-administered group. Less

最近的研究已经澄清，机械拉伸和压力超负荷会在某些组织和细胞中诱导肺损伤和HSP70。但是，尚不清楚是否在伸展的肺中诱导HSP70，例如机械通气的肺部。本研究旨在研究高峰气道压力（PAP）通气对完整大鼠肺HSP70表达的影响。将雄性Sprague-Dawley大鼠随机分配给三组之一：非通风（单独麻醉）对照组（NVC）； PAP 15 CMH_2O组（P15）;和PAP 30 CMH_2O组（P30）。在30分钟的压力控制辅助通风后，在12小时，P30组中的HSP70表达在支气管细胞和上皮下组织中显着更新，并且在整个观察期内，此更新继续进行。相比之下，NVC和P15组之间没有显着差异，尽管HSP70在所有时间点都在P15组中进行了更新。 HSP…更多的70是由高PAP通气引起的，但其特异性作用和诱导机制仍然不清楚。在大鼠肺损伤中酸诱导的肺损伤后，研究了轻度体温过低的次数对细胞间粘附分子-1（ICAM-1）的表达进行了研究。与非固定组相比，酸性大鼠中的氧合作用显着受损，但是轻度体温过低的诱导逐渐改善了氧合。 ICAM-1的表达增强了酸含酸的固定体热组。相比之下，在酸含有酸的低温组中未检测到ICAM-1及其转录本的过表达。另外，暴露于轻度体温过低后，嗜中性粒细胞的积累被明显抑制。我们的数据表明，温和的体温过低可以抑制酸诱导的肺损伤急性期嗜中性粒细胞的粘附，激活和积累，并提出一种方法可能会减少ARDS患者的持续损害。最后，我们研究了人尿胰蛋白酶抑制剂（Urinastatin UTI）对酸诱导的肺损伤的影响。已知UTI抑制肿瘤坏死因子（TNF）-A的产生，该因子可能会刺激白细胞激活。这项研究的目的是阐明UTI是否通过TNF-Aproduction抑制活化的白细胞来改善大鼠酸诱导的肺损伤。 OA给药后4小时，UTI显着改善了OA诱导的组织学变化。 OA诱导的PAO2的降低，肺血管通透性的增加以及肺组织中的MPO活性和TNF-A的水平在大鼠行政UTI中有效改善。白细胞减少症组的作用与UTI管理组中的作用相似。较少的