Ye Lu-Xia, An Ning-Chen, Huang Peng, Li Duo-Hui, Zheng Zhi-Long, Ji Hao, Li Hao, Chen Da-Qing, Wu Yan-Qing, Xiao Jian, Xu Ke, Li Xiao-Kun, Zhang Hong-Yu
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Department of Pharmacy, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Neural Regen Res. 2021 Apr;16(4):765-771. doi: 10.4103/1673-5374.295347.
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 HO. 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.
血脊髓屏障在脊髓损伤后的恢复中起着至关重要的作用。神经血管单元概念强调了大脑中神经与血管之间的关系，而在脊髓损伤研究中，血脊髓屏障对神经血管单元的影响鲜有报道。通过重物撞击建立小鼠脊髓损伤模型，然后立即在损伤部位注射血小板衍生生长因子（80μg/kg）。我们的结果表明，给予血小板衍生生长因子后，脊髓损伤、神经元凋亡和血脊髓屏障通透性降低，过度的星形胶质细胞增殖和自噬相关凋亡信号通路受到抑制，胶原蛋白合成增加，小鼠运动功能得到改善。在体外，通过暴露于200μM HO建立人脐静脉内皮细胞。在损伤前2小时，用5 ng/mL血小板衍生生长因子处理体外细胞模型。我们的结果表明，包括闭合蛋白、紧密连接蛋白5和β-连环蛋白在内的血脊髓屏障相关蛋白的表达显著降低，自噬显著减少。此外，在脊髓损伤前连续3天腹腔注射80 mg/kg自噬抑制剂氯喹可逆转血小板衍生生长因子的保护作用。我们的研究结果表明，血小板衍生生长因子可通过调节自噬促进内皮细胞修复，改善血脊髓屏障功能，并促进脊髓损伤后运动功能的恢复。动物实验于2018年7月获得中国温州医科大学动物伦理委员会批准（批准号wydw2018-0043）。
