Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.

Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.
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DOI:
10.1038/s41598-020-76401-x
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发表时间:
2020-11-12
期刊:
影响因子:
4.6
通讯作者:
Kim J
Kim J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shoaib M;Choudhary RC;Choi J;Kim N;Hayashida K;Yagi T;Yin T;Nishikimi M;Stevens JF;Becker LB;Kim J

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心脏骤停(CA)是导致死亡的主要原因之一,因此有必要建立能够准确反映人体损伤严重程度的动物模型。我们通过比较血浆代谢改变与人类患者来评估严重CA损伤的大鼠模型。从复苏后的成年人对照和CA患者,以及从基线和20分钟CA随后30分钟心肺转流复苏后的雄性Sprague-Dawley大鼠获得血浆。使用UPLC-QTOF-MS/MS进行非靶向代谢组学评价,以进行血浆代谢组学比较。在这里,我们显示了人类和我们的严重损伤大鼠模型之间的代谢共性,突出了显著的代谢功能障碍,如在(1)TCA循环代谢物,(2)色氨酸和犬尿烯酸代谢物,和(3)酰基肉毒碱,脂肪酸和磷脂代谢物中的类似改变所见。由于复苏后血浆中存在大量种间代谢相似性,我们的长期CA大鼠模型在代谢上复制了人类疾病,是转化CA研究的合适模型。
Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague–Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research.
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