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肾脏机器灌注过程中的代谢组学灌注液分析:猪为人体研究提供了合适的模型。

Metabolomic perfusate analysis during kidney machine perfusion: the pig provides an appropriate model for human studies.

作者信息

Nath Jay, Guy Alison, Smith Thomas B, Cobbold Mark, Inston Nicholas G, Hodson James, Tennant Daniel A, Ludwig Christian, Ready Andrew R

机构信息

Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom; Department of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom; School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.

Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom; Department of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom.

出版信息

PLoS One. 2014 Dec 12;9(12):e114818. doi: 10.1371/journal.pone.0114818. eCollection 2014.

Abstract

INTRODUCTION

Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs.

METHODS

Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy.

RESULTS

There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples.

CONCLUSIONS

Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies.

摘要

引言

低温机器灌注在肾脏移植方面前景广阔,需要进行实验研究以确定实现这一目标的最佳条件。猪肾被认为是实现这一目的的良好模型,并且与人体器官具有许多共同特性。然而,在这种低温缺氧条件下猪肾的代谢是否与人体器官相当尚不确定。

方法

使用LifePort肾脏转运器1.0(器官回收系统)和KPS - 1溶液,对标准标准的人肾(n = 12)和猪肾(n = 10)进行低温机器灌注。在灌注45分钟和4小时时采集灌注液样本,并使用一维1H - NMR光谱进行代谢组学分析。

结果

鉴定出的代谢物数量没有种间差异。在分析的30种代谢物中,16种(53.3%)在猪肾和人肾灌注液中的浓度相当。人肾中3 - 羟基丁酸的浓度变化率更大(p<0.001)。对于其他29种代谢物(96.7%),猪和人样本之间的浓度变化率没有差异。

结论

虽然在低温机器灌注过程中猪肾和人肾之间存在一些差异,但它们在代谢上似乎相似,并且猪似乎是人体研究的有效模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03c4/4264773/524ef477044b/pone.0114818.g001.jpg

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