Sciuto A M, Stotts R R
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, USA.
Exp Lung Res. 1998 May-Jun;24(3):273-92. doi: 10.3109/01902149809041535.
Acetylenic acids such as 5,8,11,14-eicosatetraynoic acid (ETYA), have been shown to be effective in preventing pulmonary edema formation (PEF). In phosgene-exposed guinea pigs, we examined the effects of ETYA on PEF, measured as real time lung weight gain (lwg). Pulmonary artery pressure (Ppa), airway pressure (Paw), perfusate leukotrienes (LT) C4/D4/E4/B4, and lung tissue lipid peroxidation (TBARS) were measured using the isolated, buffer-perfused lung model. Guinea pigs were challenged to 175 mg/m3 (44 ppm) phosgene for 10 minutes giving a concentration x time product of 1750 mg.min/m3 (437 ppm.min). Five minutes after removal from the exposure chamber, guinea pigs were treated, i.p., with 200 microL of 100 microM ETYA. 200 microL of 50 microM ETYA was added to the perfusate every 40 minutes, beginning at 60 minutes after start of exposure (t = 0). There were four groups in this study: air-treated, phosgene-exposed, ETYA-posttreated + phosgene, and ETYA-posttreated + air ETYA-posttreated + phosgene guinea pigs had significantly lower Ppa (P = .006), Paw (P = .009), and lwg (P = .016) compared with phosgene-exposed animals. Phosgene exposure reduced LTB4 compared with air-treated controls (P = .09). ETYA-posttreatment + phosgene had significantly increased perfusate LTB4 (P = .0006) compared with phosgene exposure only group. Total perfusate, LTC4 + LTD4 + LTE4, was not different between phosgene-exposed, air-treated or ETYA-posttreatment + phosgene over time. Posttreatment with ETYA significantly lowered TBARS formation, 206 +/- 13 versus 285 +/- 23 nmol/mg protein (P = .016), compared with phosgene-exposed lungs. Paradoxically, ETYA posttreatment decreased PEF and lipid peroxidation, but increased sulfidopeptide LT release from the lung during perfusion. We conclude that LTC4/D4/E4, and B4, may play different roles than previously thought for PEF in the isolated perfused lung model.
炔酸如5,8,11,14-二十碳四炔酸（ETYA）已被证明在预防肺水肿形成（PEF）方面有效。在光气暴露的豚鼠中，我们研究了ETYA对PEF的影响，以实时肺重量增加（lwg）来衡量。使用离体缓冲灌注肺模型测量肺动脉压（Ppa）、气道压（Paw）、灌注液中的白三烯（LT）C4/D4/E4/B4以及肺组织脂质过氧化（TBARS）。豚鼠暴露于175 mg/m³（44 ppm）光气中10分钟，浓度×时间乘积为1750 mg·min/m³（437 ppm·min）。从暴露室取出后5分钟，豚鼠腹腔注射200 μL 100 μM的ETYA。从暴露开始后60分钟（t = 0）起，每隔40分钟向灌注液中添加200 μL 50 μM的ETYA。本研究有四组：空气处理组、光气暴露组、ETYA后处理+光气组以及ETYA后处理+空气组。与光气暴露动物相比，ETYA后处理+光气组豚鼠的Ppa（P = 0.006）、Paw（P = 0.009）和lwg（P = 0.016）显著降低。与空气处理对照组相比，光气暴露使LTB4降低（P = 0.09）。与仅光气暴露组相比，ETYA后处理+光气组灌注液中的LTB4显著增加（P = 0.0006）。随着时间推移，光气暴露组、空气处理组或ETYA后处理+光气组的灌注液中总LTC4 + LTD4 + LTE4没有差异。与光气暴露的肺相比，ETYA后处理显著降低了TBARS的形成，分别为206±13与285±23 nmol/mg蛋白质（P = 0.016）。矛盾的是，ETYA后处理降低了PEF和脂质过氧化，但在灌注过程中增加了肺中硫肽LT的释放。我们得出结论，在离体灌注肺模型中，LTC4/D4/E4和B4在PEF中可能发挥与先前认为的不同的作用。
