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脊髓损伤蛋白生物标志物在大鼠中的时间分布特征及其与严重程度的相关性研究。

Temporal Profile and Severity Correlation of a Panel of Rat Spinal Cord Injury Protein Biomarkers.

机构信息

Departments of Psychiatry & Neuroscience, Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Gainesville, FL, 32611, USA.

University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.

出版信息

Mol Neurobiol. 2018 Mar;55(3):2174-2184. doi: 10.1007/s12035-017-0424-7. Epub 2017 Mar 13.

Abstract

In the USA, there are approximately 12,000 new cases of spinal cord injury (SCI) each year and some 1.2 million people living with paralysis due to SCI. Seven percent of them are paralyzed due to an accident or injury occurring while serving in the military. Here, we report a systematic study on protein biomarker candidates in a rat SCI model with either moderate or severe injury. Tissue, cerebrospinal fluid (CSF), and serum samples were obtained at 4 h, 24 h, and 7 days post-injury. The candidate biomarkers included axonal injury markers αII-spectrin breakdown products (SBDP150/145/120), neuronal cell body injury marker ubiquitin C-terminal hydrolase-L1 (UCH-L1), astrogliosis/astroglial injury markers S100 calcium-binding protein-β (S100β), glial fibrillary acidic protein (GFAP) and GFAP breakdown products (GBDPs), demyelination marker myelin basic protein (MBP), axonal injury marker phosphorylated neurofilament-H (pNF-H), and neuroinflammation marker interleukin-6 (IL-6). SBDP150/145, UCH-L1, GFAP, and S100β were found as acute biomarkers with significantly elevated levels within 24 h. GBDP44, GBDP38, and pNF-H are acute and subacute biomarkers that were found to have increased at 4 h, 24 h, and 7 days. MBP and SBDP120 were considered subacute biomarkers which were only detectable at 7 days post-injury. These results not only allow us to gain important insight into the patho-mechanisms of SCI but also showcase the possibility of using some of the protein biomarkers to track injury severity and disease progression and resolution. These biomarkers can potentially serve as tools that assist therapy development and clinical trials.

摘要

在美国,每年大约有 12000 例新的脊髓损伤(SCI)病例,约有 120 万人因 SCI 而瘫痪。其中 7%的人因在军队服役时发生意外或受伤而瘫痪。在这里,我们报告了一项在中度或重度 SCI 大鼠模型中对蛋白质生物标志物候选物的系统研究。在损伤后 4 小时、24 小时和 7 天获得组织、脑脊液(CSF)和血清样本。候选生物标志物包括轴索损伤标志物αII- spectrin 断裂产物(SBDP150/145/120)、神经元细胞体损伤标志物泛素 C 端水解酶-L1(UCH-L1)、星形胶质细胞/星形胶质细胞损伤标志物 S100 钙结合蛋白-β(S100β)、胶质纤维酸性蛋白(GFAP)和 GFAP 断裂产物(GBDPs)、脱髓鞘标志物髓鞘碱性蛋白(MBP)、轴索损伤标志物磷酸化神经丝-H(pNF-H)和神经炎症标志物白细胞介素-6(IL-6)。SBDP150/145、UCH-L1、GFAP 和 S100β 被认为是在 24 小时内显著升高的急性生物标志物。GBDP44、GBDP38 和 pNF-H 是在 4 小时、24 小时和 7 天发现的急性和亚急性生物标志物。MBP 和 SBDP120 被认为是亚急性生物标志物,仅在损伤后 7 天可检测到。这些结果不仅使我们对 SCI 的病理机制有了重要的了解,还展示了使用一些蛋白质生物标志物来跟踪损伤严重程度和疾病进展和恢复的可能性。这些生物标志物有可能成为辅助治疗开发和临床试验的工具。

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