中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 757-763.doi: 10.4103/1673-5374.295347

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

外源性血小板衍生生长因子恢复脊髓损伤后的神经血管单元

  

  • 出版日期:2021-04-15 发布日期:2020-12-22
  • 基金资助:

    中国国家自然科学基金项目（81802251，81772450，81801233）；浙江省自然科学基金项目（LQ18H150003，LY19H150001，LQ18H090011，LQ20C200015）；浙江省医药高等重点学科开放项目（YKFJ3-011）

Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury

Lu-Xia Ye1, #, Ning-Chen An1, #, Peng Huang2, #, Duo-Hui Li1, Zhi-Long Zheng1, Hao Ji3, Hao Li4, Da-Qing Chen5, Yan-Qing Wu3, Jian Xiao1, Ke Xu3, *, Xiao-Kun Li1, *, Hong-Yu Zhang1, *#br#   

  1. 1 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China;  2 Department of Pharmacy, Ruian People’s Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China;  3 Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang Province, China;  4 Department of Orthopedics Surgery, Lishui People’s Hospital, The sixth affiliated hospital of Wenzhou Medical University, Lishui, Zhejiang Province, China;  5 Department of Emergency, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • Online:2021-04-15 Published:2020-12-22
  • Contact: Ke Xu, PhD, godxu1987@wzu.edu.cn; Xiao-Kun Li, PhD, lixk1964@163.com; Hong-Yu Zhang, PhD, st_hyz@126.com.
  • Supported by:
    This study was partly supported by research grants from the National Natural Science Foundation of China, Nos. 81802251 (to KX), 81772450 (to HYZ) and 81801233 (to YQW); the Natural Science Foundation of Zhejiang Province of China, Nos. LQ18H150003 (to KX), LY19H150001 (to DQC), LQ18H090011 (to YQW) and LQ20C200015 (to HJ); and the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences, No. YKFJ3-011 (to KX).

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摘要：

脊髓损伤后,血脊髓屏障起着十分重要的作用｡神经血管单元强调大脑中神经与血管之间的关系,而很少有研究关注脊髓损伤后血脊髓屏障对神经血管单元的作用｡(1)实验通过重物打击法建立脊髓损伤大鼠模型,即刻于损伤部位注射血小板衍生生长因子80 μg/kg｡结果发现,血小板衍生生长因子干预后,脊髓损伤大鼠脊髓损伤及神经元凋亡减轻,血脊髓屏障通透性下降,星形胶质细胞过度增殖受到抑制,胶原蛋白合成增加,自噬相关凋亡信号通路受到抑制,运动功能显著改善;(2)以人脐静脉内皮细胞暴露于200 μM H2O2建立体外模型,在损伤前2h给予血小板衍生生长因子5 ng/mL预处理｡结果发现血脊髓屏障相关蛋白Occludin,Claudin 5和β-catenin的表达明显恢复,细胞自噬明显减少;(3)同时血小板衍生生长因子的保护作用,可被脊髓损伤前连续3d给予80 mg/kg自噬抑制剂氯喹所逆转;(4)结果提示,血小板衍生生长因子能够通过调节自噬来促进内皮细胞的修复,改善血脊髓屏障的功能,促进脊髓损伤后运动功能的恢复｡实验于2018年7月经温州医科大学伦理委员会批准,批准号wydw2018-0043｡

https://orcid.org/0000-0003-1412-5659 (Hong-Yu Zhang) 

关键词: 中枢神经系统, 脊髓, 血小板衍生生长因子, 脊髓损伤, 自噬, 神经血管单元, 运动, 血脊髓屏障

Abstract: The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies. Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with platelet-derived growth factor (80 μg/kg) at the injury site. Our results showed that after platelet-derived growth factor administration, spinal cord injury, neuronal apoptosis, and blood-spinal cord barrier permeability were reduced, excessive astrocyte proliferation and the autophagy-related apoptosis signaling pathway were inhibited, collagen synthesis was increased, and mouse locomotor function was improved. In vitro, human umbilical vein endothelial cells were established by exposure to 200 μM H2O2. At 2 hours prior to injury, in vitro cell models were treated with 5 ng/mL platelet-derived growth factor. Our results showed that expression of blood-spinal cord barrier-related proteins, including Occludin, Claudin 5, and β-catenin, was significantly decreased and autophagy was significantly reduced. Additionally, the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine, an autophagy inhibitor, for 3 successive days prior to spinal cord injury. Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy, improve the function of the blood-spinal cord barrier, and promote the recovery of locomotor function post-spinal cord injury. Approval for animal experiments was obtained from the Animal Ethics Committee, Wenzhou Medical University, China (approval No. wydw2018-0043) in July 2018.

Key words: autophagy, blood-spinal cord barrier, central nervous system, locomotor function, neurovascular unit, platelet-derived growth factor, spinal cord, spinal cord injury