1514 Jefferson Highway, Department of Neurocritical Care, Neurosurgery and Neurology, University of Queensland, Ochsner Clinical School, Ochsner Medical Center, New Orleans, LA, USA; Institute of Translational Research, Ochsner Medical Center, New Orleans, LA, USA; Neuroscience Center of Excellence, Louisiana State University Health New Orleans, School of Medicine, New Orleans, LA, USA.
Institute of Translational Research, Ochsner Medical Center, New Orleans, LA, USA.
Biochimie. 2022 Apr;195:16-18. doi: 10.1016/j.biochi.2021.12.017. Epub 2022 Jan 4.
Little is known of the lipid anti-inflammatory mediators, docosanoids, in intracerebral hemorrhage (ICH). We aim to characterize the abundance of the docosanoid, Neuroprotectin D1 (NPD1), in ICH patients. Blood samples (whole blood in PAXgene-blood-RNA tubes and plasma) were collected from consecutive patients with acute spontaneous ICH within 48 h of admission. A liquid-liquid lipid extraction was used for liquid chromatography-mass spectrometry (LC-MS/MS) and analyzed using MassLynx Mass Spectrometry Software with results normalized to internal standards. RNA was extracted from PAXgene-blood-RNA tubes for 15-LOX-1 gene expression, a critical enzyme in NPD1 synthesis. Demographic and clinical data were collected. Outcome measures included 90-day modified-rankin-score. Sixteen patients were included in the study with a mean age of 62.5years (SD13.5). Three abundant isomers were detected and analyzed - NPD1, PDX, and an uncharacterized isomer designated as NPD1-C. NPD1 levels were higher in patients with 90-day MRS 0-3 (49.63pg/mL SD43.78 vs. 1.88pg/mL SD1.7 p = 0.0012). ROC-AUC analysis showed an NPD1 cutoff of 2.9pg/mL differentiated 90-day MRS 0-3 (sensitivity 100%, specificity 88.89%, AUC 0.98 p = 0.0002). A Spearman correlation demonstrated an inverse relationship with NPD1 and 90-day MRS (rho -7.392 p = 0.0011). 15-LOX-1 gene was almost undetectable in patients with MRS 4-6. Though not significant, NPD1 levels were higher in patients <65 years, ICH volume <30 ml, and non-whites. NPD1 was abundant and significantly higher in ICH patients with MRS 0-3.15-LOX-1 was significantly under-expressed in patients with MRS 4-6. Early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology.
关于在脑出血(ICH)中的脂类抗炎介质——二十二碳六烯酸,我们知之甚少。我们旨在研究神经保护素 D1(NPD1)在 ICH 患者中的含量。在发病后 48 小时内,连续采集急性自发性 ICH 患者的血液样本(PAXgene-blood-RNA 管中的全血和血浆)。采用液-液脂质提取法进行液相色谱-质谱联用(LC-MS/MS)分析,并使用 MassLynx Mass Spectrometry Software 进行分析,结果用内标物进行标准化。从 PAXgene-blood-RNA 管中提取 RNA,用于 15-LOX-1 基因表达的研究,该基因是 NPD1 合成的关键酶。收集人口统计学和临床数据。预后指标包括 90 天改良Rankin 评分。该研究共纳入 16 例患者,平均年龄为 62.5 岁(标准差 13.5 岁)。检测并分析了三种丰度较高的异构体 - NPD1、PDX 和一种未鉴定的异构体,命名为 NPD1-C。90 天 MRS 0-3 的患者 NPD1 水平较高(49.63pg/ml 标准差 43.78 与 1.88pg/ml 标准差 1.7,p=0.0012)。ROC-AUC 分析显示,NPD1 截断值为 2.9pg/ml 可区分 90 天 MRS 0-3(敏感性 100%,特异性 88.89%,AUC 0.98,p=0.0002)。Spearman 相关性分析显示,NPD1 与 90 天 MRS 呈负相关(rho-7.392,p=0.0011)。MRS 4-6 的患者 15-LOX-1 基因几乎无法检测到。尽管没有统计学意义,但 MRS<65 岁、ICH 体积<30ml 和非白人患者的 NPD1 水平较高。NPD1 在 MRS 0-3 的 ICH 患者中含量丰富且显著升高。MRS 4-6 的患者 15-LOX-1 表达显著降低。NPD1 的早期合成和丰度可能是 ICH 病理生理学中的一种重要保护介质。