Sudo E, Fukuchi Y, Ishida K, Matsuse T, Nagase T, Teramoto S, Higashimoto Y, Jo C, Matsui H, Oka T
Department of Geriatrics, Faculty of Medicine, University of Tokyo.
Nihon Ronen Igakkai Zasshi. 1993 Dec;30(12):1032-8. doi: 10.3143/geriatrics.30.1032.
The purpose of this study is to evaluate chemical and pathological changes of the lung and to elucidate the role of TNF alpha and elastase in acute lung injury induced by HCl or lipopolysaccharide (LPS). Anesthetized rats were injected with pH 1.4 0.7 ml/kg body weight of HCl and 0.5 mg/kg body weight (BW) of LPS (E. coli) into the lung. Acute tracheal injury model (Mendelson Syndrome) were made. Control animals received only saline. Animals were sacrificed 1, 6, or 12 hours after the HCl or LPS or HCl and LPS injection, bronchoalveolar-lavage (BAL) was performed in the same way in control and experimental groups. The other animals which were treated as well were excised by histology. There was neither increase in TNF alpha-production nor increase in neutrophils resulting from HCl injection only. Elastase-like activity was not detected in animals treated only with HCl. However, 1 hour after LPS injection, the production of TNF alpha (37.0 +/- 8.0 Units/ml) was significantly greater than that of the control group (12.1 +/- 4.2 Units/ml) in BALF. Six hours after HCl and LPS injection, the concentration of elastase-like activity (0.023 +/- 0.002 nM) was significantly greater than that of the LPS group (0.011 +/- 0.001 nM). Only patches of intraalveolar hemorrhage and elevation of fibrin was observed in the HCl injected rats at 1 hour after injection. Six hours after LPS injection, the alveolar spaces were filled with large amounts of neutrophils. These findings suggest that TNF alpha and elastase play a significant role in HCl and LPS-induced acute lung injury.
本研究的目的是评估肺部的化学和病理变化，并阐明肿瘤坏死因子α（TNFα）和弹性蛋白酶在盐酸（HCl）或脂多糖（LPS）诱导的急性肺损伤中的作用。将麻醉的大鼠经肺注射pH 1.4的HCl 0.7 ml/kg体重和LPS（大肠杆菌）0.5 mg/kg体重，制成急性气管损伤模型（门德尔松综合征）。对照动物仅接受生理盐水。在注射HCl或LPS或HCl与LPS后1、6或12小时处死动物，对照组和实验组以相同方式进行支气管肺泡灌洗（BAL）。对其他同样处理的动物进行组织学切除。仅注射HCl后，TNFα的产生和中性粒细胞均未增加。仅用HCl处理的动物未检测到类弹性蛋白酶活性。然而，注射LPS 1小时后，BALF中TNFα的产生（37.0±8.0单位/ml）显著高于对照组（12.1±4.2单位/ml）。注射HCl和LPS 6小时后，类弹性蛋白酶活性浓度（0.023±0.002 nM）显著高于LPS组（0.011±0.001 nM）。注射HCl的大鼠在注射后1小时仅观察到肺泡内少量出血和纤维蛋白升高。注射LPS 6小时后，肺泡腔内充满大量中性粒细胞。这些发现表明，TNFα和弹性蛋白酶在HCl和LPS诱导的急性肺损伤中起重要作用。
