Bahado-Singh Ray O, Syngelaki Argyro, Mandal Rupsari, Graham Stewart F, Akolekar Ranjit, Han Beomsoo, Bjondahl Trent C, Dong Edison, Bauer Samuel, Alpay-Savasan Zeynep, Turkoglu Onur, Ogunyemi Dotun, Poon Liona C, Wishart David S, Nicolaides Kypros H
a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
b Harris Birthright Research Centre for Fetal Medicine , Division of Women's Health, King's College Hospital , London , UK.
J Matern Fetal Neonatal Med. 2017 Mar;30(6):658-664. doi: 10.1080/14767058.2016.1185411. Epub 2016 Aug 28.
Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE.
NMR-based metabolomics analysis was performed on 29 cases of late-PE and 55 unaffected controls. In order to achieve sufficient statistical power to perform the pathway analysis, these cases were combined with a group of previously analyzed specimens, 30 late-PE cases and 60 unaffected controls. Specimens from both groups of cases and controls were collected in the same clinical centers during the same time period. In addition, NMR analyses were performed in the same lab and using the same techniques.
We identified abnormalities in branch chain amino acids (valine, leucine and isoleucine) and propanoate, glycolysis, gluconeogenesis and ketone body metabolic pathways. The results suggest insulin resistance and metabolic syndrome, mitochondrial dysfunction and disturbance of energy metabolism, oxidative stress and lipid dysfunction in the pathogenesis of late PE and suggest a potential role for agents that reduce insulin resistance in PE.
Branched chain amino acids are known markers of insulin resistance and strongly predict future diabetes development. The analysis provides independent evidence linking insulin resistance and late-PE and suggests a potentially important therapeutic role for pharmacologic agents that reduce insulin resistance for late-PE.
我们的主要目的是对孕早期孕妇血清进行代谢组学通路分析，以深入了解晚发型子痫前期（late-PE）的发病机制，从而确定子痫前期可能的治疗靶点。
对29例晚发型子痫前期患者和55例未受影响的对照者进行基于核磁共振的代谢组学分析。为了获得足够的统计效力以进行通路分析，将这些病例与一组先前分析过的样本合并，即30例晚发型子痫前期病例和60例未受影响的对照者。两组病例和对照者的样本均在同一临床中心同一时间段采集。此外，核磁共振分析在同一实验室使用相同技术进行。
我们发现支链氨基酸（缬氨酸、亮氨酸和异亮氨酸）和丙酸、糖酵解、糖异生及酮体代谢途径存在异常。结果表明在晚发型子痫前期发病机制中存在胰岛素抵抗和代谢综合征、线粒体功能障碍及能量代谢紊乱、氧化应激和脂质功能障碍，并提示降低胰岛素抵抗的药物在子痫前期可能发挥潜在作用。
支链氨基酸是已知的胰岛素抵抗标志物，能强烈预测未来糖尿病的发生。该分析提供了独立证据，将胰岛素抵抗与晚发型子痫前期联系起来，并表明降低胰岛素抵抗的药物对晚发型子痫前期可能具有重要的治疗作用。
