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合成表面活性剂中的磷脂组成对接受表面活性剂治疗的早产新生兔的潮气量和肺泡稳定性至关重要。

Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits.

作者信息

Calkovska Andrea, Linderholm Bim, Haegerstrand-Björkman Marie, Pioselli Barbara, Pelizzi Nicola, Johansson Jan, Curstedt Tore

机构信息

Laboratory for Surfactant Research, Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.

出版信息

Neonatology. 2016;109(3):177-85. doi: 10.1159/000442874. Epub 2016 Jan 13.

Abstract

BACKGROUND

The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years.

OBJECTIVES

To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome.

METHODS

Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated.

RESULTS

Treatment with Curosurf or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (VT) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small VT, but after addition of both analogues VT was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on VT and LGV as Curosurf.

CONCLUSIONS

Phospholipid composition is important for VT while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding VT and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.

摘要

背景

用于治疗肺部疾病的合成表面活性剂的研发已进行多年。

目的

在呼吸窘迫综合征动物模型中,研究磷脂混合物与表面活性蛋白B(SP - B)和表面活性蛋白C(SP - C)类似物联合使用对肺功能的影响。

方法

将含有/不含SP - B和/或SP - C类似物的天然及合成磷脂混合物滴入通气的早产新生兔体内。对肺功能进行评估。

结果

使用固尔苏或固尔苏中的磷脂与SP - B和SP - C类似物联合治疗,结果相似。用成年兔肺或肝中的磷脂与二棕榈酰磷脂酰胆碱(DPPC)和棕榈酰油酰磷脂酰甘油(POPG)联合治疗,潮气量(VT)远高于生理水平,但仅当这些磷脂与SP - B和SP - C类似物联合时,才能在呼气末实现肺泡稳定性。用蛋黄卵磷脂与DPPC混合,无论有无POPG,潮气量都较小,但加入两种类似物后,潮气量仅略低,肺气体容积(LGV)与使用固尔苏时相似。用1 - 棕榈酰 - 2 - 油酰 - sn - 甘油 - 3 - 磷酸胆碱和1 - 棕榈酰 - 2 - 亚油酰 - sn - 甘油 - 3 - 磷酸胆碱替代蛋黄卵磷脂(≥99%卵磷脂),并将它们与DPPC、POPG以及各2%的SP - B和SP - C类似物联合使用,得到一种完全合成的表面活性剂,其对VT和LGV的影响与固尔苏相似。

结论

磷脂组成对VT很重要,而SP - B和SP - C类似物可增加呼气末的肺泡稳定性。在未使用呼气末正压通气的早产新生兔动物模型中,由不饱和及饱和磷脂酰胆碱、POPG以及SP - B和SP - C类似物组成的合成表面活性剂在VT和LGV方面具有与固尔苏相似的活性。

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