First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Pulm Pharmacol Ther. 2010 Feb;23(1):43-7. doi: 10.1016/j.pupt.2009.10.004. Epub 2009 Oct 14.
The present study was performed to investigate the role of exogenous surfactant on hydrochloric acid (HCL) - induced lung injury in rats. Six-week-old male Sprague-Dawley rats were anesthetized by intraperitoneal injection of pentobarbital sodium (40mg/kg) and HCL (0.1N, 2mL/kg) or normal saline (NS, 2mL/kg) was instilled into the trachea. Thirty minutes after HCL instillation, surfactant at a dose of 60mg (=2mL)/body or NS (2mL) was instilled into the rat lungs. Animals in another experimental group were also treated with the same dose of surfactant supplement 2hours after the first administration. Bronchoalveolar lavage fluid (BALF) was obtained 5hours after HCL instillation. In BALF, increases in total nuclear cell counts, neutrophil counts, optical density at 412nm as an indicator of pulmonary hemorrhage, neutrophil elastase activity, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) induced by HCL instillation were significantly attenuated by surfactant treatment. The wet-to-dry weight (W/D) ratio in the lung and partial oxygen tension (P(O2)) were also estimated; surfactant treatment significantly attenuated the W/D ratio and improved deteriorated P(O2) induced by HCL. Additional surfactant supplementation did not show further beneficial effects on HCL-induced lung injury compared with a single treatment. These results suggest that surfactant shows an anti-inflammatory effect on acid lung injury in rats but the beneficial effects may be dose limited.
本研究旨在探讨外源性表面活性剂对盐酸(HCl)诱导的大鼠肺损伤的作用。6 周龄雄性 Sprague-Dawley 大鼠经腹腔注射戊巴比妥钠(40mg/kg)麻醉后,将 HCl(0.1N,2mL/kg)或生理盐水(NS,2mL/kg)注入气管。在 HCl 注入 30 分钟后,将 60mg(=2mL)/体的表面活性剂或 NS(2mL)注入大鼠肺部。另一实验组的动物在第一次给药后 2 小时也接受了相同剂量的表面活性剂补充治疗。在 HCl 注入后 5 小时获得支气管肺泡灌洗液(BALF)。在 BALF 中,总核细胞计数、中性粒细胞计数、作为肺出血指标的 412nm 处光密度、中性粒细胞弹性蛋白酶活性、白蛋白浓度和细胞因子诱导的中性粒细胞趋化因子(CINC)均显著增加表面活性剂处理可减轻 HCL 诱导的增加。还估计了肺的湿重/干重(W/D)比和部分氧分压(P(O2));表面活性剂处理可显著减轻 W/D 比并改善 HCL 引起的 P(O2)恶化。与单次治疗相比,额外的表面活性剂补充治疗并未显示对 HCL 诱导的肺损伤有进一步的有益作用。这些结果表明,表面活性剂对大鼠酸肺损伤具有抗炎作用,但有益作用可能是剂量限制的。