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成年小鼠中合成与天然治疗性肺表面活性剂的代谢。

Metabolism of a synthetic compared with a natural therapeutic pulmonary surfactant in adult mice.

机构信息

Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Department of Biochemistry and Molecular Biology, Faculty of Biology, Hospital 12 de Octubre Research Institute, Complutense University, Madrid, Spain.

出版信息

J Lipid Res. 2018 Oct;59(10):1880-1892. doi: 10.1194/jlr.M085431. Epub 2018 Aug 14.

DOI:10.1194/jlr.M085431
PMID:30108154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6168297/
Abstract

Secreted pulmonary surfactant phosphatidylcholine (PC) has a complex intra-alveolar metabolism that involves uptake and recycling by alveolar type II epithelial cells, catabolism by alveolar macrophages, and loss up the bronchial tree. We compared the in vivo metabolism of animal-derived poractant alfa (Curosurf) and a synthetic surfactant (CHF5633) in adult male C57BL/6 mice. The mice were dosed intranasally with either surfactant (80 mg/kg body weight) containing universally C-labeled dipalmitoyl PC (DPPC) as a tracer. The loss of [UC]DPPC from bronchoalveolar lavage and lung parenchyma, together with the incorporation of C-hydrolysis fragments into new PC molecular species, was monitored by electrospray ionization tandem mass spectrometry. The catabolism of CHF5633 was considerably delayed compared with poractant alfa, the hydrolysis products of which were cleared more rapidly. There was no selective resynthesis of DPPC and, strikingly, acyl remodeling resulted in preferential synthesis of polyunsaturated PC species. In conclusion, both surfactants were metabolized by similar pathways, but the slower catabolism of CHF5633 resulted in longer residence time in the airways and enhanced recycling of its hydrolysis products into new PC species.

摘要

分泌性肺表面活性物质磷脂酰胆碱（PC）在肺泡内具有复杂的代谢过程，包括肺泡 II 型上皮细胞摄取和再循环、肺泡巨噬细胞分解代谢以及通过支气管树丢失。我们比较了动物源性肺表面活性剂 poractant alfa（Curosurf）和合成表面活性剂（CHF5633）在成年雄性 C57BL/6 小鼠体内的代谢情况。小鼠经鼻腔给予含有普遍 C 标记的二棕榈酰磷脂酰胆碱（DPPC）作为示踪剂的两种表面活性剂（80mg/kg 体重）。通过电喷雾串联质谱监测[UC]DPPC 从支气管肺泡灌洗液和肺实质中的丢失，以及 C 水解产物掺入新的 PC 分子种类的情况。与 poractant alfa 相比，CHF5633 的分解代谢明显延迟，其水解产物清除得更快。没有 DPPC 的选择性再合成，而且令人惊讶的是，酰基重塑导致多不饱和 PC 种类的优先合成。总之，两种表面活性剂都通过类似的途径代谢，但 CHF5633 较慢的分解代谢导致其在气道中的停留时间更长，并增强了其水解产物重新合成新的 PC 种类的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/845a1ff12deb/1880fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/b68e50b7a89d/1880fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/386b1837589b/1880fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/9530c8fa65d1/1880fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/03c64d6dcade/1880fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/a5481e620e39/1880fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/c6d88e758165/1880fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/7292ed2fc7b5/1880fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/845a1ff12deb/1880fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/b68e50b7a89d/1880fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/2b2718ad22f6/1880fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/386b1837589b/1880fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/9530c8fa65d1/1880fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/03c64d6dcade/1880fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/a5481e620e39/1880fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/c6d88e758165/1880fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/7292ed2fc7b5/1880fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/6168297/845a1ff12deb/1880fig9.jpg

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本文引用的文献

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Langmuir. 2017 Aug 15;33(32):7929-7939. doi: 10.1021/acs.langmuir.7b01177. Epub 2017 Aug 3.
2
A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome.一项针对患有呼吸窘迫综合征的早产儿的新型富含表面活性蛋白B和表面活性蛋白C的合成表面活性剂（CHF5633）的首次人体临床研究。
Arch Dis Child Fetal Neonatal Ed. 2017 Nov;102(6):F497-F503. doi: 10.1136/archdischild-2017-312722. Epub 2017 May 2.
3
Restoring pulmonary surfactant membranes and films at the respiratory surface.
严重新型冠状病毒肺炎感染患者雾化吸入表面活性剂后的快速磷脂周转：一项随机临床试验
Am J Respir Crit Care Med. 2022 Feb 15;205(4):471-473. doi: 10.1164/rccm.202110-2279LE.
4
Pulmonary Surfactants: a New Therapeutic Target in Asthma.肺表面活性剂：哮喘治疗的新靶点。
Curr Allergy Asthma Rep. 2020 Sep 11;20(11):70. doi: 10.1007/s11882-020-00968-8.
5
Surfactant replacement therapy: from biological basis to current clinical practice.表面活性物质替代疗法：从生物学基础到当前临床实践。
Pediatr Res. 2020 Aug;88(2):176-183. doi: 10.1038/s41390-020-0750-8. Epub 2020 Jan 11.
6
Tracing exogenous surfactant in vivo in rabbits by the natural variation of C.通过 C 的自然变异在兔体内追踪外源性表面活性剂。
Respir Res. 2019 Jul 18;20(1):158. doi: 10.1186/s12931-019-1124-9.
7
Helical side chain chemistry of a peptoid-based SP-C analogue: Balancing structural rigidity and biomimicry.基于肽类的 SP-C 类似物的螺旋侧链化学：平衡结构刚性和仿生特性。
Biopolymers. 2019 Jun;110(6):e23277. doi: 10.1002/bip.23277. Epub 2019 Apr 10.
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4
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Pediatr Res. 2017 Feb;81(2):369-375. doi: 10.1038/pr.2016.231. Epub 2016 Nov 3.
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Biochim Biophys Acta. 2016 Aug;1863(8):2124-34. doi: 10.1016/j.bbamcr.2016.04.028. Epub 2016 May 4.
6
Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants.用于预防和治疗早产儿呼吸窘迫综合征的动物源性表面活性剂的比较。
Cochrane Database Syst Rev. 2015 Dec 21;2015(12):CD010249. doi: 10.1002/14651858.CD010249.pub2.
7
Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.血清、胆固醇和低密度脂蛋白对肺表面活性物质膜功能及结构的影响。
J Oleo Sci. 2014;63(12):1333-49. doi: 10.5650/jos.ess14071. Epub 2014 Nov 18.
8
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Respir Res. 2014 Nov 7;15(1):128. doi: 10.1186/s12931-014-0128-8.
9
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Chem Phys Lipids. 2015 Jan;185:153-75. doi: 10.1016/j.chemphyslip.2014.09.002. Epub 2014 Sep 28.
10
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Biochim Biophys Acta. 2014 Jun;1838(6):1568-85. doi: 10.1016/j.bbamem.2014.01.028. Epub 2014 Feb 11.