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作为一种支持性平台技术的三维基质胶构建体中生长的内皮细胞的31P磁共振波谱分析:II. 抗炎药物对磷酸代谢物水平的影响。

31P magnetic resonance spectroscopy of endothelial cells grown in three-dimensional matrigel constructs as an enabling platform technology: II. The effect of anti-inflammatory drugs on phosphometabolite levels.

作者信息

Ringel I, Lecht S, Sterin M, Lelkes P I, Lazarovici P

机构信息

Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

出版信息

Endothelium. 2008 Sep-Oct;15(5-6):299-307. doi: 10.1080/10623320802487874.

Abstract

In the accompanying study, the authors presented phosphometabolite patterns of endothelial cells grown under three-dimensional (3D) conditions using (31)P magnetic resonance spectroscopy (MRS). Here the authors describe the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), using this enabling platform technology, which is relevant for evaluating drug effects in tissue-engineered endothelial constructs. Treatment with indomethacin significantly changed the phosphometabolite fingerprint in this endothelial model, by, respectively, increasing (81%) and decreasing (42%) glycerophosphocholine (GPC) and phosphomonoesters (PM). Furthermore, a safer approach using a NSAID prodrug was also demonstrated in this study with a indomethacin phospholipid-derived prodrug (DP-155). Like the parental drug, DP-155 increased and decreased the levels of GPC and PM by 100% and 20%, respectively. These changes represent useful biomarkers to monitor NSAID effects on endothelized tissue-engineered constructs for the purpose of controlling endothelial cell survival and inflammation upon implantation.

摘要

在随附的研究中,作者使用³¹P磁共振波谱(MRS)展示了在三维(3D)条件下生长的内皮细胞的磷酸代谢物模式。在此,作者描述了使用这种赋能平台技术的非甾体抗炎药(NSAIDs)的作用,这对于评估组织工程化内皮构建物中的药物作用具有重要意义。在这个内皮模型中,吲哚美辛治疗显著改变了磷酸代谢物指纹图谱,分别使甘油磷酸胆碱(GPC)增加了81%,磷酸单酯(PM)减少了42%。此外,本研究还展示了一种使用NSAID前药的更安全方法,即吲哚美辛磷脂衍生前药(DP - 155)。与母体药物一样,DP - 155分别使GPC和PM的水平增加了100%和减少了20%。这些变化是有用的生物标志物,可用于监测NSAIDs对内皮化组织工程构建物的影响,以便在植入时控制内皮细胞存活和炎症。

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