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Therapeutic Effect of Intravenous Infusion of Perfluorocarbon Emulsion on LPS-Induced Acute Lung Injury in Rats

机译:静脉输注全氟化碳乳剂对LPS诱导的大鼠急性肺损伤的治疗作用

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摘要

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC), a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide). In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS) induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group), 18 rats were treated with LPS by intratracheal instillation (LPS group) and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group). The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2) and lung wet-dry weight ratio (W/D) of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN) induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice.
机译:急性肺损伤(ALI)及其更严重的形式,急性呼吸窘迫综合征(ARDS)是重症监护室中死亡的主要原因。尽管在研究和临床医学上进行了广泛的努力,但这些疾病的死亡率仍然很高。全氟化碳(PFC)是一种称为液体通风介质的化合物,能够溶解大量生理上重要的气体(主要是氧气和二氧化碳)。在这项研究中,我们旨在研究静脉内注射PFC乳液对脂多糖(LPS)诱导的大鼠ALI的影响,并阐明其作用机理。 42只Wistar大鼠随机分为三组:气管内滴入生理盐水6只(对照组),气管内滴入LPS 18只(LPS组),另18只大鼠经股静脉先行PFC注入LPS(LPS + PFC组)。盐水滴注后6小时,将对照组的大鼠处死。在暴露于LPS的2、4和6小时时,在每个时间点处死LPS组的6只大鼠和LPS + PFC组的6只大鼠。通过分析每只大鼠的肺部病理,血液中的氧分压(PaO2)和肺干重比(W / D),我们发现静脉内注射PFC可以显着减轻LPS引起的急性肺损伤。此外,我们发现,通过体内PFC处理,LPS诱导的肺髓过氧化物酶(MPO),内皮细胞间粘附分子1(ICAM-1)和多形核中性粒细胞(PMN)CD11b的表达显着降低。我们的结果表明,静脉输注PFC可以抑制PMN渗透到肺组织,这已被证明是ALI / ARDS的核心发病机制。因此,我们的研究为临床上使用PFC静脉输注预防和治疗ALI / ARDS提供了理论基础。

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