Lee Tsung-Heng, Cheng Chih-Ning, Chao Hsi-Chun, Lee Ching-Hua, Kuo Ching-Hua, Tang Sung-Chun, Jeng Jiann-Shing
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
J Formos Med Assoc. 2022 Jan;121(1 Pt 1):43-50. doi: 10.1016/j.jfma.2021.01.006. Epub 2021 Jan 24.
BACKGROUND/PURPOSE: Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes.
Plasma samples were collected from patients with AIS at <48 and 48-72 h post stroke and from nonstroke controls. The levels of S1P and ceramides with different fatty acyl chain lengths were measured by the ultra-high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). A poor functional outcome was defined as a modified Rankin Scale (mRS) score ≥2 at 3 months after AIS.
The results showed that S1P and very-long-chain ceramides were significantly decreased in AIS patients (n = 87; poor outcome, 56.3%) compared to nonstroke controls (n = 30). In contrast, long-chain ceramides were significantly increased in AIS patients. More importantly, higher levels of Cer(d18:1/18:0), Cer(d18:1/20:0), and Cer(d18:1/22:0) at 48-72 h were significantly associated with poor functional outcomes after adjusting for potential clinical confounders, including age, sex, hypertension, and National Institutes of Health Stroke Scale score at admission.
Our study supported the dynamic metabolism of sphingolipids after the occurrence of AIS. Ceramides could be potential prognostic markers for patients with AIS.
背景/目的：鞘脂是真核细胞膜的主要成分，在细胞调节过程中起关键作用。我们最近在实验性中风动物模型中的结果表明，鞘脂会因急性缺血性脑损伤而发生变化。本研究旨在调查急性缺血性中风（AIS）患者血浆中1-磷酸鞘氨醇（S1P）和神经酰胺的水平及其与功能结局的关系。
在中风后<48小时和48-72小时从AIS患者以及非中风对照者中采集血浆样本。采用超高压液相色谱-电喷雾电离串联质谱法（UHPLC-ESI-MS/MS）测定不同脂肪酰基链长度的S1P和神经酰胺水平。功能结局不良定义为AIS后3个月改良Rankin量表（mRS）评分≥2分。
结果显示，与非中风对照者（n = 30）相比，AIS患者（n = 87；结局不良者占56.3%）的S1P和超长链神经酰胺显著降低。相反，AIS患者的长链神经酰胺显著增加。更重要的是，在调整了包括年龄、性别、高血压和入院时美国国立卫生研究院卒中量表评分等潜在临床混杂因素后，48-72小时时较高水平的Cer（d18:1/18:0）、Cer（d18:1/20:0）和Cer（d18:1/22:0）与不良功能结局显著相关。
我们的研究支持AIS发生后鞘脂的动态代谢。神经酰胺可能是AIS患者潜在的预后标志物。
