中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (4): 676-681.doi: 10.4103/1673-5374.266924

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

创伤性脑损伤患者唾液细胞外囊泡的炎症基因谱

  

  • 出版日期:2020-04-15 发布日期:2020-05-28
  • 基金资助:

    美国国家心脏,肺和血液研究所的资助;美国国立卫生研究院美国国立普通医学科学研究所提供支持(COBRE);美国国立卫生研究院转化科学促进中心和罗德岛州普罗维登斯市罗德岛医院血液学/肿瘤科支持

Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma

Yan Cheng1, Mandy Pereira1, Neha P. Raukar2, John L. Reagan1, Mathew Quesenberry1, Laura Goldberg1, Theodor Borgovan1,#br# W Curt LaFrance Jr3, Mark Dooner1, Maria Deregibus5, Giovanni Camussi5, Bharat Ramratnam4, Peter Quesenberry1#br#   

  1. 1 Department of Medicine, Division of Hematology/Oncology, Rhode Island Hospital, Providence, RI, USA
    2 Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA
    3 Department of Psychiatry and Neurology, Rhode Island Hospital, Providence, RI, USA
    4 Department of Medicine, Division of Infectious Diseases, Rhode Island Hospital, Providence, RI, USA
    5 Department of Medical Sciences, University of Turin, Torino TO, Italy
  • Online:2020-04-15 Published:2020-05-28
  • Contact: Mandy Pereira, MS,mpereira7@lifespan.org.
  • Supported by:
    This project was supported by the National Heart, Lungs, and Blood Institute Grant #T32HL116249 (to PQ). Additional support from the National Institute of General Medical Sciences of the NIH through grant (COBRE) #P20GM103468 Flow Cytometry Core (to PQ), National Center for Advancing Translational Sciences of the NIH grant #5UH3TROOO880-05 (to PQ) and institutional support through the Division of Hematology/oncology, Rhode Island Hospital, Providence, RI.

摘要:

目前没有可用于创伤性脑损伤诊断的可靠生物标志物。有研究显示,受损细胞释放到生物体液中的细胞外囊泡可分离出潜在用于诊断创伤性脑损伤的生物标志物。作者推测,创伤性脑损伤患者唾液细胞外囊泡中的基因与健康者不同,可用于了解创伤性脑损伤患者的受伤情况。研究招募了19名参与者,包括7名非创伤性脑损伤健康对照者,6例脑震荡患者,6例患者在急诊科就诊的24h内受伤的创伤性脑损伤患者。以TaqMan Human Inflammation阵列对参与者唾液细胞外囊泡进行实时PCR分析。结果显示,与健康对照者相比,急诊科患者中有9个基因表达上调: LOX5, ANXA3, CASP1, IL2RG, ITGAM, ITGB2, LTA4H, MAPK14, TNFRSF1A,脑震荡患者中有13个基因表达上调: ADRB1, ADRB2, BDKRB1, HRH1, HRH2, LTB4R2, LTB4R, PTAFR, CYSLTR1, CES1, KLK1, MC2R, PTGER3,且各患者组具有独特的特征。当各组相互比较时,15个炎症基因的改变有统计学意义。研究结果表明,炎性生物标志物可用于创伤性脑损伤的诊断和严重程度评估。研究于20151218日和201669日经机构审查委员会批准(0078-12和#4093-16)

orcid: 0000-0002-3999-9048 (Mandy Pereira)

关键词: 慢性创伤性脑病, 急诊科, 细胞外囊泡, , 门诊脑震荡诊所, 实时PCR分析, 唾液, 创伤性脑损伤

Abstract: At present, there is no reliable biomarker for the diagnosis of traumatic brain injury (TBI). Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential biomarkers for diagnosis of TBI and evaluation of TBI severity. We hypothesize that the genetic profile of salivary extracellular vesicles in patients with head trauma differs from that in uninjured subjects. Findings from this hypothesis would help investigate the severity of TBI. This study included 19 subjects, consisting of seven healthy controls who denied history of head trauma, six patients diagnosed with concussion injury from an outpatient concussion clinic, and six patients with TBI who received treatment in the emergency department within 24 hours after injury. Real-time PCR analysis of salivary extracellular vesicles in participants was performed using TaqMan Human Inflammation array. Gene expression analysis revealed nine upregulated genes in emergency department patients (LOX5, ANXA3, CASP1, IL2RG, ITGAM, ITGB2, LTA4H, MAPK14, and TNFRSF1A) and 13 upregulated genes in concussion clinic patients compared with healthy participants (ADRB1, ADRB2, BDKRB1, HRH1, HRH2, LTB4R2, LTB4R, PTAFR, CYSLTR1, CES1, KLK1, MC2R, and PTGER3). Each patient group had a unique profile. Comparison between groups showed that 15 inflammation-related genes had significant expression change. Our results indicate that inflammation biomarkers can be used for diagnosis of TBI and evaluation of disease severity. This study was approved by the Institutional Review Board on December 18, 2015 (approval No. 0078-12) and on June 9, 2016 (approval No. 4093-16).

Key words: chronic traumatic encephalopathy, emergency department, extracellular vesicles, inflammation, outpatient concussion clinic, real-time PCR analysis, saliva, traumatic brain injury