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气管内给药后新生兔和成年兔对珂立苏的摄取与降解

Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits.

作者信息

Alberti A, Pettenazzo A, Enzi G B, Palamidese A, Mapp C, Ventura P, Baritussio A

机构信息

Dept of Internal Medicine, University of Padova, Italy.

出版信息

Eur Respir J. 1998 Aug;12(2):294-300. doi: 10.1183/09031936.98.12020294.

Abstract

This paper examines the removal from the airways of Curosurf, a commercial surfactant derived from porcine lungs, administered at pharmacological concentrations to newborn or adult animals. Curosurf was labelled by the addition of radioactive dipalmitoyl phosphatidylcholine (DPPC) and administered intratracheally to newborn and adult rabbits at a dose of 200 mg x kg(-1) body weight. The disappearance of DPPC from the airways and its appearance in alveolar macrophages, lung parenchyma, lamellar bodies, serum, liver, kidneys and brain was then studied for 24-48 h. The in vitro degradation of Curosurf DPPC by alveolar macrophages was also studied. During the first 3 h after instillation, large amounts of Curosurf left the airways and became associated with tissue, indicating that it mixed rapidly with the endogenous pools of surfactant. A fraction of administered DPPC became associated with the lamellar bodies, suggesting that Curosurf can be recycled. Curosurf administration did not stop the secretion of endogenous surfactant. Very little intact radioactive DPPC could be recovered at any time in alveolar macrophages, however, macrophages have the ability, in vitro, to degrade Curosurf. Newborn rabbits lose Curosurf from the lungs at a slower rate than adult rabbits. One and two days after instillation, organic extracts from the liver, kidney, brain and serum contained small but measurable amounts of radioactivity. These results indicate that Curosurf rapidly enters the pathways of surfactant metabolism and that alveolar macrophages may play an important role in the catabolism of Curosurf.

摘要

本文研究了以药理浓度给予新生或成年动物的猪肺来源商业表面活性剂珂立苏(Curosurf)从气道中的清除情况。通过添加放射性二棕榈酰磷脂酰胆碱(DPPC)对珂立苏进行标记,并以200 mg x kg(-1)体重的剂量经气管内给予新生和成年兔。然后在24 - 48小时内研究气道中DPPC的消失情况及其在肺泡巨噬细胞、肺实质、板层小体、血清、肝脏、肾脏和大脑中的出现情况。还研究了肺泡巨噬细胞对珂立苏DPPC的体外降解情况。滴注后的最初3小时内,大量珂立苏离开气道并与组织结合,表明它迅速与内源性表面活性剂池混合。一部分给予的DPPC与板层小体结合,提示珂立苏可被再循环利用。给予珂立苏并未停止内源性表面活性剂的分泌。然而,在肺泡巨噬细胞中任何时候都只能回收极少量完整的放射性DPPC,不过巨噬细胞在体外有降解珂立苏的能力。新生兔肺部珂立苏的清除速度比成年兔慢。滴注后1天和2天,肝脏、肾脏、大脑和血清的有机提取物中含有少量但可测量的放射性。这些结果表明珂立苏迅速进入表面活性剂代谢途径,并且肺泡巨噬细胞可能在珂立苏的分解代谢中起重要作用。

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