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

最近的研究表明，机械拉伸和压力过载可引起肺损伤和某些组织和细胞的HSP70。然而，目前尚不清楚HSP70是否会在受到拉伸的肺中被诱导，例如机械通气下的肺。本研究旨在探讨高峰气道压力通气（PAP）对完整大鼠肺HSP70表达的影响。雄性Sprague-Dawley大鼠随机分为三组：非通气（单独麻醉）对照组（NVC）；PAP 15 cmH_2O组（P15）；PAP 30 cmH_2O组（P30）。在压力控制辅助通气30 min后，P30组细支气管细胞和上皮下组织HSP70表达在12 h时显著上调，并在整个观察期内持续上调。相比之下，NVC组和P15组之间没有显著差异，尽管P15组在所有时间点都上调了HSP70。高PAP通气诱导的HSP超过70例，但其具体作用和诱导机制尚不清楚。随后研究亚低温对酸致肺损伤大鼠细胞间粘附分子-1（ICAM-1）表达及中性粒细胞积累的影响。与未灌注组相比，酸灌注组大鼠的氧合明显受损，但诱导亚低温逐渐改善氧合。正常灌酸组ICAM-1表达增强。相比之下，在低温灌酸组没有检测到ICAM-1及其转录物的过表达。此外，暴露于轻度低温后，中性粒细胞的积累被明显抑制，而与酸的灌注无关。我们的数据表明，在酸致肺损伤的急性期，亚低温可以抑制中性粒细胞的粘附、激活和积累，并提示一种可能潜在地减少ARDS患者持续损伤的方法。最后，我们研究了人尿胰酶抑制剂（Urinastatin， UTI）对酸致肺损伤的作用。众所周知，UTI可以抑制肿瘤坏死因子（TNF）的产生，而TNF能有效地刺激白细胞的活化。本研究的目的是阐明UTI是否通过tnf -a的产生抑制活化的白细胞，从而改善大鼠酸诱导的肺损伤。在给药后4小时，UTI显著改善OA诱导的组织学改变。大鼠UTI后，oa诱导的PaO2减少，肺血管通透性增加，肺组织中MPO活性和TNF-a水平显著提高。白细胞减少组的效果与尿路感染组相似。少

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