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The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats
Molecules ( IF 4.2 ) Pub Date : 2020-09-23 , DOI: 10.3390/molecules25194356
Maros Kolomaznik , Jana Kopincova , Zuzana Nova , Juliana Topercerova , Ivan Zila , Pavol Mikolka , Petra Kosutova , Katarina Matasova , Henrieta Skovierova , Marian Grendar , Daniela Mokra , Andrea Calkovska

The study aimed to prove the hypothesis that exogenous surfactant and an antibiotic polymyxin B (PxB) can more effectively reduce lipopolysaccharide (LPS)-induced acute lung injury (ALI) than surfactant treatment alone, and to evaluate the effect of this treatment on the gene expression of surfactant proteins (SPs). Anesthetized rats were intratracheally instilled with different doses of LPS to induce ALI. Animals with LPS 500 μg/kg have been treated with exogenous surfactant (poractant alfa, Curosurf®, 50 mg PL/kg b.w.) or surfactant with PxB 1% w.w. (PSUR + PxB) and mechanically ventilated for 5 hrs. LPS at 500 μg/kg increased lung edema, oxidative stress, and the levels of proinflammatory mediators in lung tissue and bronchoalveolar lavage fluid (BALF). PSUR reduced lung edema and oxidative stress in the lungs and IL-6 in BALF. This effect was further potentiated by PxB added to PSUR. Exogenous surfactant enhanced the gene expression of SP-A, SP-B, and SP-C, however, gene expression for all SPs was reduced after treatment with PSUR + PxB. In mechanically ventilated rats with LPS-induced ALI, the positive effect of exogenous surfactant on inflammation and oxidative stress was potentiated with PxB. Due to the tendency for reduced SPs gene expression after surfactant/PxB treatment topical use of PxB should be considered with caution.

中文翻译:

改性猪表面活性剂单独或与多粘菌素 B 联合对 LPS 攻击和机械通气成年大鼠肺稳态的影响

该研究旨在证明外源性表面活性剂和抗生素多粘菌素 B (PxB) 可以比单独的表面活性剂治疗更有效地减少脂多糖 (LPS) 诱导的急性肺损伤 (ALI) 的假设,并评估这种治疗对基因的影响表面活性蛋白 (SP) 的表达。麻醉大鼠气管内灌注不同剂量的 LPS 以诱导 ALI。LPS 500 μg/kg 的动物已用外源性表面活性剂(poractant alfa,Curosurf®,50 mg PL/kg bw)或含 PxB 1% ww 的表面活性剂(PSUR + PxB)处理并机械通气 5 小时。500 μg/kg 的 LPS 会增加肺水肿、氧化应激以及肺组织和支气管肺泡灌洗液 (BALF) 中促炎介质的水平。PSUR 减少肺水肿和肺中的氧化应激以及 BALF 中的 IL-6。将 PxB 添加到 PSUR 进一步增强了这种效果。外源性表面活性剂增强了 SP-A、SP-B 和 SP-C 的基因表达,然而,在用 PSUR + PxB 处理后,所有 SP 的基因表达都降低了。在机械通气的 LPS 诱导的 ALI 大鼠中,外源性表面活性剂对炎症和氧化应激的积极作用被 PxB 增强。由于表面活性剂/PxB 治疗后局部使用 PxB 后 SPs 基因表达降低的趋势,应谨慎考虑。PxB 增强了外源性表面活性剂对炎症和氧化应激的积极作用。由于表面活性剂/PxB 治疗后局部使用 PxB 后 SPs 基因表达降低的趋势,应谨慎考虑。PxB 增强了外源性表面活性剂对炎症和氧化应激的积极作用。由于表面活性剂/PxB 治疗后局部使用 PxB 后 SPs 基因表达降低的趋势,应谨慎考虑。
更新日期:2020-09-23
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