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富含重组人超氧化物歧化酶的改良猪肺表面活性剂治疗实验性胎粪吸入综合征。

Modified porcine surfactant enriched by recombinant human superoxide dismutase for experimental meconium aspiration syndrome.

机构信息

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin (JFM CU), Department of Physiology JFM CU, Slovakia; Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin (JFM CU), Biomedical Center Martin JFM CU, Slovakia.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin (JFM CU), Biomedical Center Martin JFM CU, Slovakia.

出版信息

Life Sci. 2018 Jun 15;203:121-128. doi: 10.1016/j.lfs.2018.04.036. Epub 2018 Apr 21.

DOI:10.1016/j.lfs.2018.04.036
PMID:29684443
Abstract

AIMS

Combination of exogenous surfactant with antioxidant enzyme recombinant human superoxide dismutase (rhSOD) was tested in the treatment of experimental meconium aspiration syndrome as oxidative processes play key role in its pathogenesis.

MATERIAL AND METHODS

Young New Zealand rabbits were instilled by saline (Sal group) or by meconium suspension (Mec group). Some of meconium-instilled animals were treated by surfactant alone (Surf group) or surfactant in combination with rhSOD (Surf + SOD group) and oxygen-ventilated for 5 h. PaO/FiO, oxygenation index, oxygen saturation, PaCO, ventilation efficiency index and alveolar-arterial gradient were evaluated every hour; post mortem, cells in bronchoalveolar lavage were counted, inflammatory and oxidative markers were assessed using ELISA in lung tissue homogenates.

KEY FINDINGS

Exogenous surfactant combined with rhSOD improved oxygenation during the first hour after the treatment more than surfactant alone (p = 0.039 to 0.0001 vs. Mec and Surf group). Amelioration was also seen in CO elimination (p = 0.049 to 0.0096 vs. Mec group), alveolar-arterial gradient diminution (p = 0.024 to 0.0019 vs. Mec and Surf group), prevention of oxidative damage and cytokine production (p = 0.049 to 0.002 vs. Mec group).

SIGNIFICANCE

It seems that inhibition of oxidative signalization may be strong supporting factor in surfactant treatment of MAS.

摘要

目的

外源性表面活性剂与抗氧化酶重组人超氧化物歧化酶(rhSOD)联合应用于实验性胎粪吸入综合征的治疗,因为氧化过程在其发病机制中起关键作用。

材料与方法

新西兰幼兔经生理盐水(Sal 组)或胎粪混悬液(Mec 组)滴注。部分胎粪滴注动物单独用表面活性剂(Surf 组)或表面活性剂联合 rhSOD(Surf+SOD 组)治疗,并进行氧通气 5 小时。每小时评估 PaO/FiO、氧合指数、氧饱和度、PaCO、通气效率指数和肺泡-动脉梯度;死后,对支气管肺泡灌洗液中的细胞进行计数,采用 ELISA 法检测肺组织匀浆中的炎症和氧化标志物。

主要发现

外源性表面活性剂联合 rhSOD 在治疗后第 1 小时比单独使用表面活性剂(与 Mec 和 Surf 组相比,p=0.039 至 0.0001)更能改善氧合。CO 清除率也得到改善(与 Mec 组相比,p=0.049 至 0.0096),肺泡-动脉梯度降低(与 Mec 和 Surf 组相比,p=0.024 至 0.0019),氧化损伤和细胞因子产生得到预防(与 Mec 组相比,p=0.049 至 0.002)。

意义

抑制氧化信号似乎是表面活性剂治疗 MAS 的一个强有力的支持因素。

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