中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (12): 2134-2140.doi: 10.4103/1673-5374.241462

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

创伤性脑损伤7 d内生长因子水平动态变化可评价患者的预后预后结局

  

  • 收稿日期:2018-09-10 出版日期:2018-12-15 发布日期:2018-12-15
  • 基金资助:

    国家自然科学基金（81330029）(JNZ)，（ 81501057）(YT)；天津市高等教育委员会科学技术发展基金（2016YD02）(YW)；天津市卫生计生委中医药重点领域技术项目基金（2018001）(ZGW)

Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

Shuai Zhou1, 2, 3, 4, 5, Dong-Pei Yin2, 3, 4, 5, Yi Wang2, 3, 4, 5, Ye Tian2, 3, 4, 5, Zeng-Guang Wang2, 3, 4, 5, Jian-Ning Zhang2, 3, 4, 5   

  1. 1 Department of Intensive Care Unit, Tianjin Medical University General Hospital, Tianjin, China
    2 Tianjin Neurological Institute, Tianjin, China
    3 Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
    4 Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
    5 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
  • Received:2018-09-10 Online:2018-12-15 Published:2018-12-15
  • Contact: Zeng-Guang Wang, MD, wzgforrest@163.com; Jian-Ning Zhang, MD, PhD, jianningzhang@hotmail.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81330029 (to JNZ), 81501057 (to YT); the Science & Technology Development Fund of Tianjin Education Commission for Higher Education in China, No. 2016YD02 (to YW); the Technology Program Fund of Tianjin Health and Family Planning Commission for the Key Field of Traditional Chinese Medicine, No. 2018001 (to ZGW).

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摘要：

创伤性脑损伤(TBI)可导致神经功能障碍和死亡，并且总体结局不尽相同。生长因子如血管生成素1，血管内皮生长因子和粒细胞集落刺激因子在血管生成和神经功能的调节中发挥重要作用，研究者设计以此探索TBI后血清生长因子水平与长期预后之间的关系。纳入TBI患者55例，在TBI后1，3，7 d采集血样，设39例健康对照者的血样为对照组。采用ELISA法测定血清中血管内皮生长因子、血管生成素-1和粒细胞集落刺激因子水平。TBI患者随访3个月 GOSE评分>5分归类为预后良好，GOSE评分为1-5分归类为预后不良。数据显示，与健康对照相比，患者在TBI后7 d内各生长因子水平均显著增加。相对于预后不良患者，预后良好患者TBI后1，7 d的血清血管生成素-1水平和TBI后7 d的粒细胞集落刺激因子水平显著升高，然而相对于预后良好组，预后不良组患者TBI后7 d血清血管内皮生长因子水平显著升高。ROC结果提示，TBI后7 d的血清血管内皮生长因子水平低于1333 pg/mL，粒细胞集落刺激因子水平＞447.2 pg/mL或血清血管生成素-1水平＞90.6 ng/mL更有可能具有良好预后结局。上述随访数据表明，在TBI急性期(7 d内)，血清促血管生成素-1和粒细胞集落刺激因子水平升高者，血管内皮生长因子水平降低者，预后结局较好。实验已经于中国临床试验中心注册（注册号：ChiCTR1800018251，注册时间：2018-09-07）。

orcid:0000-0002-7505-4500(Shuai Zhou)
        0000-0002-7290-0994(Jian-Ning Zhang)

 

关键词: 创伤性脑损伤, 血管内皮生长因子, 血管生成素-1, 粒细胞集落刺激因子, 转归, 继发性脑损伤, 血脑屏障, 脑水肿, 急性期, 神经再生, 临床试验

Abstract:

Traumatic brain injury (TBI) can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating factor (G-CSF), play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended (GOSE). Patients having a GOSE score of > 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1–5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI (within 7 days). This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800018251) on September 7, 2018.

Key words: nerve regeneration, traumatic brain injury, vascular endothelial growth factor, angiopoietin-1, granulocyte-colony stimulating factor, outcomes, secondary brain injuries, blood-brain barrier, brain edema, acute phase, clinical trial, neural regeneration