Department of Pediatric Emergency Medicine and Critical Care Medicine, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, P.R. China.
Department of Pediatric Emergency Medicine and Critical Care Medicine, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, P.R. China.
Thromb Res. 2015 Jul;136(1):131-8. doi: 10.1016/j.thromres.2015.04.018. Epub 2015 Apr 22.
Locally increased expression of plasminogen activator inhibitor-1 (PAI-1) in acute lung injury (ALI) is largely responsible for fibrin deposition in the alveolae and lung microvasculature. In vitro, nitric oxide (NO) effectively suppresses the ischemic induction of PAI-1. We aimed to investigate the effects of inhaled NO on PAI-1 expression in ALI in a rat model with and without hyperoxia.
Healthy adult rats were primed with lipopolysaccharide (LPS) via an intraperitoneal challenge followed by a second dose of LPS given intratracheally to induce ALI (LPS group), whereas the control groups were given sterile saline. All groups were allocated to subgroups according to gas exposure: NO (20 parts per million, NO), 95% oxygen (O), both (ONO), or room air (A). At 4h, 24h, 48h (after 4h or 24h exposure to the various gases, 24h gas intervention and then observation until 48h), the rat lungs were processed and PAI-1 protein and mRNA expression, histopathological lung injury scores and fibrin deposition were evaluated.
At 4 and 24h, inhaled NO caused the PAI-1 mRNA levels in the LPS-NO and LPS-ONO subgroups to decrease compared with the untreated LPS subgroups. At 48h, higher PAI-1 mRNA levels than those of the corresponding control subgroup were only observed in the LPS-O subgroup, and these values were lower in the LPS-ONO subgroup than in the LPS-O subgroup. The trends of the PAI-1 protein levels mirrored those of PAI-1 mRNA. At 48h, PAI-1 protein levels in the LPS-NO and LPS-ONO subgroups were decreased compared with those in the untreated LPS subgroups. The histopathological lung injury scores and fibrin deposition in LPS subgroups that inhaled NO showed a decreasing trend compared with the untreated LPS subgroups.
Inhaled NO can suppress elevated PAI-1 expression in rats with ALI induced by endotoxin. Although exposure to high-concentration oxygen prolongs the duration of PAI-1 mRNA overexpression in ALI, inhaled NO can reduce this effect and alleviate both fibrin deposition and lung injury.
纤溶酶原激活物抑制剂-1（PAI-1）在急性肺损伤（ALI）中的局部表达增加在很大程度上导致了肺泡和肺微血管中纤维蛋白的沉积。在体外，一氧化氮（NO）可有效抑制缺血诱导的 PAI-1。我们旨在研究吸入 NO 对 LPS 诱导的 ALI 大鼠模型中 PAI-1 表达的影响，同时研究高浓度氧对 ALI 中 PAI-1 表达的影响。
健康成年大鼠经腹腔内注射脂多糖（LPS）预激，然后经气管内给予第二次 LPS 剂量，以诱导 ALI（LPS 组），而对照组给予无菌生理盐水。所有组均根据气体暴露进行亚组分配：NO（20ppm，NO）、95%氧气（O）、两者（ONO）或室内空气（A）。在 4h、24h、48h（4h 或 24h 暴露于各种气体后、24h 气体干预然后观察至 48h）时，处理大鼠肺脏，评估 PAI-1 蛋白和 mRNA 表达、组织病理学肺损伤评分和纤维蛋白沉积。
在 4h 和 24h 时，与未处理的 LPS 亚组相比，LPS-NO 和 LPS-ONO 亚组的吸入 NO 导致 PAI-1mRNA 水平降低。在 48h 时，仅在 LPS-O 亚组中观察到高于相应对照组的 PAI-1mRNA 水平，并且 LPS-ONO 亚组中的 PAI-1mRNA 水平低于 LPS-O 亚组。PAI-1 蛋白水平的趋势与 PAI-1mRNA 水平一致。在 48h 时，与未处理的 LPS 亚组相比，LPS-NO 和 LPS-ONO 亚组的 PAI-1 蛋白水平降低。与未处理的 LPS 亚组相比，吸入 NO 的 LPS 亚组的组织病理学肺损伤评分和纤维蛋白沉积呈下降趋势。
吸入 NO 可抑制内毒素诱导的 ALI 大鼠升高的 PAI-1 表达。虽然高浓度氧暴露延长了 ALI 中 PAI-1mRNA 过度表达的持续时间，但吸入 NO 可降低这种作用，并减轻纤维蛋白沉积和肺损伤。
