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靶向代谢组学分析揭示中风后氨基酸改变与功能恢复不良之间的关联。

Targeted Metabolomic Profiling Reveals Association Between Altered Amino Acids and Poor Functional Recovery After Stroke.

作者信息

Wang Xin, Liu Tao, Song Haixin, Cui Shaoyang, Liu Gang, Christoforou Andrea, Flaherty Patrick, Luo Xun, Wood Lisa, Wang Qing Mei

机构信息

Stroke Biological Recovery Laboratory, Spaulding Rehabilitation Hospital, Boston, MA, United States.

Department of Rehabilitation, Clinical Medical College, Yangzhou University, Yangzhou, China.

出版信息

Front Neurol. 2020 Jan 24;10:1425. doi: 10.3389/fneur.2019.01425. eCollection 2019.

Abstract

Amino acids have been shown to be among the most important metabolites to be altered following stroke; however, they are a double-edged sword with regard to regulating hemostasis. In this study, we conducted a targeted metabolomic study to examine the association between serum levels of amino acids and functional recovery after stroke. Three hundred and fifty-one patients with stroke admitted to an acute rehabilitation hospital were screened, and 106 patients were selected based on inclusion and exclusion criteria. Recruited patients were stratified using Montebello Rehabilitation Factor Score (MRFS) efficiency. We selected the top ( = 20, 19%) and bottom ( = 20, 19%) of MRFS efficiency for metabolomic analysis. A total of 21 serum amino acids levels were measured using ultra high performance liquid chromatography and mass spectrometry. The normalized data were analyzed by multivariate approaches, and the selected potential biomarkers were combined in different combinations for prediction of stroke functional recovery. The results demonstrated that there were significant differences in leucine-isoleucine, proline, threonine, glutamic acid, and arginine levels between good and poor recovery groups. In the training (0.952) and test (0.835) sets, metabolite biomarker panels composed of proline, glutamic acid, and arginine had the highest sensitivity and specificity in distinguishing good recovery from poor. In particular, arginine was present in the top 10 combinations of the average area under the receiver operating characteristic curve (AUC) test set. Our findings suggest that amino acids related to energy metabolism and excitotoxicity may play an important role in functional recovery after stroke. Therefore, the level of serum arginine has predictive value for the recovery rate after stroke.

摘要

氨基酸已被证明是中风后发生改变的最重要的代谢物之一;然而,它们在调节止血方面是一把双刃剑。在本研究中,我们开展了一项靶向代谢组学研究,以检验血清氨基酸水平与中风后功能恢复之间的关联。对一家急性康复医院收治的351例中风患者进行了筛查,并根据纳入和排除标准选取了106例患者。采用蒙特贝洛康复因子评分(MRFS)效率对入选患者进行分层。我们选取MRFS效率最高的前20例(占19%)和最低的后20例(占19%)进行代谢组学分析。使用超高效液相色谱和质谱法测定了总共21种血清氨基酸水平。对标准化数据采用多变量方法进行分析,并将选定的潜在生物标志物以不同组合方式进行合并,以预测中风功能恢复情况。结果表明,恢复良好组与恢复较差组之间的亮氨酸 - 异亮氨酸、脯氨酸、苏氨酸、谷氨酸和精氨酸水平存在显著差异。在训练集(0.952)和测试集(0.835)中,由脯氨酸、谷氨酸和精氨酸组成的代谢物生物标志物组在区分恢复良好与恢复较差方面具有最高的敏感性和特异性。特别是,精氨酸在受试者操作特征曲线(AUC)测试集的平均曲线下面积前10种组合中出现。我们的研究结果表明,与能量代谢和兴奋性毒性相关的氨基酸可能在中风后功能恢复中发挥重要作用。因此,血清精氨酸水平对中风后的恢复率具有预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0faf/7001531/b0464fa5a113/fneur-10-01425-g0001.jpg

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