PDF(Pubmed)
Abstract：
Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.
摘要：
海水溺水引起的急性肺损伤（SD-ALI）是一种威胁生命的疾病，其特征是肺泡毛细血管通透性增加，过度的炎症反应，和难治性低氧血症。全氟化碳（PFCs）是生物相容性化合物，具有化学和生物惰性，缺乏作为氧载体的毒性，可以减轻体内外的肺损伤。我们研究的目的是探讨PFCs的汽化是否可以降低犬SD-ALI的严重程度，并研究其潜在机制。18只比格犬随机分为3组:海水溺水(SW),全氟化碳(PFC),和对照组。SW组犬气管内给予海水建立动物模型。PFC组中的狗用汽化的PFC处理。基于探针的共聚焦激光显微内镜（pCLE）在3小时进行。容积空气指数(VAI)，病理变化,和湿-干(W/D)肺组织比率进行评估。血红素加氧酶-1(HO-1)的表达,核呼吸因子-1（NRF1），通过定量实时聚合酶链反应（qRT-PCR）和免疫组织学化学确定了NOD样受体家族的pyrin结构域-3（NLRP3）炎性体。SW组表现出较高的肺损伤评分和W/D比值，与对照组相比，VAI较低，用PFCs治疗可以逆转肺损伤评分的变化，W/D比和VAI。PFCs使NLRP3炎性体失活，并减少caspase-1，白介素-1β（IL-1β）的释放，和白细胞介素-18（IL-18）通过增强HO-1和NRF1的表达。我们的结果表明，PFC的汽化可以通过HO-1/NRF1途径使NLRP3炎性体失活来减弱SD-ALI。
