INDUCTION OF HEAT-STRESS PROTEINS IS ASSOCIATED WITH DECREASED MORTALITY IN AN ANIMAL-MODEL OF ACUTE LUNG INJURY
INDUCTION OF HEAT-STRESS PROTEINS IS ASSOCIATED WITH DECREASED MORTALITY IN AN ANIMAL-MODEL OF ACUTE LUNG INJURY
复制标题
DOI：
10.1164/ajrccm/147.1.177
复制
发表时间：
1993-01-01
期刊：
影响因子：
--
通讯作者：
SLUTSKY, AS
中科院分区：
文献类型：
--
作者：
VILLAR, J;EDELSON, JD;SLUTSKY, AS
在先前描述的急性肺损伤动物模型中，这项研究检验了短暂的全身热疗将减少肺损伤和/或死亡率的假设。正常成年SD大鼠随机分为加热组(n=40)和假加热组(n=49)。加热的动物在气管内注入磷脂酶A2前18小时升温至41-42摄氏度。在磷脂酶A2暴露48h后，比较两组的死亡率、PaO2、AAP(O2)、肺湿重/干重比、肺泡炎性细胞数和肺组织病理学。与未加热的动物相比，加热损伤的动物死亡率更低，肺损伤更少：死亡率(0对27%，p<；0.001)；AAP(O2)(22+/-3vs36+/-15 mm Hg，p<；0.002)；肺灌洗细胞计数(5.3x106vs16.9+/-7x106/ml，p<；0.002)；肺湿/干重比(4.1+/-0.6vs5.1+/-0.7p<；0.025)；实质肺损伤分数(0.10vs0.51p<；0.001)。Northern和Western分析热休克蛋白(HSP70)的转录和翻译。热休克1h后肺组织HSP70mRNA表达升高。在全身热疗后12~72小时，HSP72蛋白水平高于基线水平，但在假加热动物中无明显变化。这些数据表明，热预处理与诱导HSP72蛋白合成有关，可减轻实验性肺损伤的组织损伤和死亡率。
This study examined the hypothesis that transient, whole-body hyperthermia would reduce lung damage and/or mortality in a previously described animal model of acute lung injury. Normal, adult Sprague-Dawley rats were randomly assigned either to a heated (n = 40) or to a sham-heated (n = 49) group. Heated animals were warmed to 41 to 42-degrees-C 18 h before intratracheal instillation of phospholipase A2. Forty-eight hours after phospholipase A2 exposure, the two groups were compared in a blinded fashion for mortality rate, Pa(O2), AaP(O2), lung wet/dry weight ratio, alveolar inflammatory cell number, and lung histopathology. Heated, injured animals exhibited a reduced mortality rate and less lung damage than did unheated animals: mortality (zero versus 27%, p < 0.001); AaP(O2) (22 +/- 3 versus 36 +/- 15 mm Hg, p < 0.002); lung lavage cell counts (5.3 +/- 3 versus 16.9 +/- 7 x 106/ml, p < 0.05); lung wet/dry weight ratio (4.1 +/- 0.6 versus 5.1 +/- 0.7, p < 0.025); parenchymal lung injury fraction (0.10 versus 0.51, p < 0.001). Transcription and translation of heat shock proteins (HSP70) were examined by Northern and Western analysis. Pulmonary tissue HSP70 mRNA was elevated 1 h after heating. HSP72 protein levels were increased over baseline levels between 12 and 72 h after whole-body hyperthermia, but they were unchanged in sham-heated animals. These data indicate that thermal pretreatment associated with the induction of HSP72 protein synthesis, attenuates tissue damage and mortality in experimental lung injury.