Oldham K T, Guice K S, Stetson P S, Wolfe R R
Department of Surgery, Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0245.
J Surg Res. 1989 Nov;47(5):397-402. doi: 10.1016/0022-4804(89)90090-5.
Sepsis is characterized by Adult Respiratory Distress Syndrome (ARDS)-like pulmonary dysfunction largely attributed to alveolar capillary endothelial cell injury which causes increased microvascular permeability and interstitial edema formation. In addition, quantitative and qualitative abnormalities of the pulmonary surfactant system may be important features of some clinical and experimental lung injuries. This study was designed to investigate the relationship of bacteremia and endotoxemia to pulmonary surfactant production in vivo. A technique for estimation of pulmonary surfactant phospholipid synthesis measuring incorporation of a stable isotope precursor [( 2-13C]acetate) into dipalmitoylphosphatidylcholine (DPPC) in alveolar lavage fluid was developed. Male 350 g Sprague-Dawley rats had placement of central venous catheters. After overnight recovery, sublethal bacteremia (Escherichia coli, 1 x 10(8) organisms, iv) and sublethal endotoxemia (Difco; 10 mg/kg, iv) were induced. Both were associated with lung microvascular permeability increases consistent with capillary endothelial injury. Eight-hour infusions of [2-13C]acetate were given. After sacrifice, bronchoalveolar washings and lung tissue were obtained and [2-13C] incorporation into lavage and lung DPPC was measured by gas chromatography mass spectroscopy. Endotoxin-treated animals had a 21.5% reduction in label incorporation into DPPC [1.215 +/- 0.145 APE (%) sham versus 0.954 +/- 0.144 APE (%) experimental, P greater than 0.05] and bacteremic animals had a 56.9% diminution of [2-13C]acetate incorporation [1.215 +/- 0.145 APE (%) sham versus 0.524 +/- 0.56 APE (%) experimental, P less than 0.05]. Bacteremia-induced dysfunction of alveolar type II epithelial cells manifested as diminished alveolar surfactant phospholipid production may be a contributing factor to sepsis-induced respiratory failure.
脓毒症的特征是出现类似成人呼吸窘迫综合征（ARDS）的肺功能障碍，这主要归因于肺泡毛细血管内皮细胞损伤，该损伤会导致微血管通透性增加和间质水肿形成。此外，肺表面活性物质系统的定量和定性异常可能是一些临床和实验性肺损伤的重要特征。本研究旨在调查菌血症和内毒素血症与体内肺表面活性物质产生之间的关系。开发了一种通过测量稳定同位素前体[（2-13C）乙酸盐]掺入肺泡灌洗液中二棕榈酰磷脂酰胆碱（DPPC）来估算肺表面活性物质磷脂合成的技术。对体重350克的雄性Sprague-Dawley大鼠置入中心静脉导管。过夜恢复后，诱导亚致死性菌血症（大肠杆菌，1×10（8）个菌体，静脉注射）和亚致死性内毒素血症（Difco；10毫克/千克，静脉注射）。两者均与肺微血管通透性增加相关，这与毛细血管内皮损伤一致。给予[2-13C]乙酸盐8小时输注。处死动物后，获取支气管肺泡灌洗液和肺组织，并通过气相色谱-质谱法测量[2-13C]掺入灌洗液和肺DPPC的情况。内毒素处理的动物中，标记物掺入DPPC的量减少了21.5%[假手术组为1.215±0.145 APE（%），实验组为0.954±0.144 APE（%），P>0.05]，菌血症动物中[2-13C]乙酸盐掺入量减少了56.9%[假手术组为1.215±0.145 APE（%），实验组为0.524±0.56 APE（%），P<0.05]。菌血症诱导的肺泡Ⅱ型上皮细胞功能障碍表现为肺泡表面活性物质磷脂产生减少，这可能是脓毒症诱导的呼吸衰竭的一个促成因素。
