中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1834-1840.doi: 10.4103/1673-5374.363183

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

抑制tau蛋白可促进损伤脊髓的恢复

  

  • 出版日期:2023-08-15 发布日期:2023-02-24
  • 基金资助:
    研究受国家自然科学基金（81801907）；深圳市科学技术委员会（JCYJ20180307145215811）；中山大学青年教师培养项目（19ykpy11）和深圳市三明市医学工程的支持

Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress

Guo-Liang Chen1, 2, 3, #, Kai Sun4, #, Xi-Zhe Liu3, #, Kui-Leung Tong2, 3, Zi-Juan Chen5, Lu Yu5, *, Ning-Ning Chen2, *, Shao-Yu Liu2, 3   

  1. 1Department of Orthopedic Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, China; 2Guangdong Provincial Biomedical Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China; 3Guangdong Provincial Key Laboratory of Orthopedics and Traumatology /Orthopedic Research Institute, Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 4Department of Orthopedic Surgery, Jiujiang University Affiliated Hospital, Jiujiang, Jiangxi Province, China; 5Department of Clinical Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China
  • Online:2023-08-15 Published:2023-02-24
  • Contact: Ning-Ning Chen, PhD, MD, chennn8@mail.sysu.edu.cn; Lu Yu, PhD, MD, yulu26@mail.sysu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81801907 (to NNC), Shenzhen Committee of Science and Technology, No. JCYJ20180307145215811 (to NNC), Sun Yat-sen University Youth Teacher Training Project, No.19ykpy11 (to NNC) and Sanming Project of Medicine in Shenzhen, No. SZSM201911002 (to SYL).

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摘要：

脊髓损伤后，脑脊液中高磷酸化tau浓度增加，并与损伤严重程度相关。抑制tau蛋白被认为是许多中枢神经系统疾病如创伤性脑损伤和阿尔茨海默病的有效疗法；然而，抑制tau蛋白是否在脊髓损伤的治疗中起作用仍不清楚。实验在脊髓损伤中心使用siRNA干扰脊髓损伤大鼠tau蛋白的合成。首先证实抑制tau蛋白可充分下调炎症介质肿瘤坏死因子-α，白细胞介素6和白细胞介素1β的水平，增加激活的小胶质细胞极化，即从M1促炎表型到M2抗炎表型的转变，并减少脊髓损伤后急性噬菌体中的活性氧物质。此外，抑制tau蛋白后，脊髓损伤中心周围残留神经细胞的存活和神经元和轴突再生显著增强，减少胶质瘢痕，从而改善创伤性脊髓损伤的功能恢复。以上结果说明抑制tau蛋白可以减轻脊髓损伤后的神经炎症和氧化应激反应，改善脊髓损伤的预后。

https://orcid.org/0000-0002-4576-2311 (Ning-Ning Chen); https://orcid.org/0000-0003-3851-9687 (Lu Yu)

Abstract: After spinal cord injury, the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase, and levels of both correlate with injury severity. Tau inhibition is considered effective therapy for many central nervous system diseases, including traumatic brain injury and Alzheimer’s disease. However, whether it can play a role in the treatment of spinal cord injury remains unclear. In this study, the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression. We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin-6 and interleukin-1β. It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype, and reduced the amount of reactive oxygen species in the acute phase. Furthermore, the survival of residual neural cells around the injury epicenter, and neuronal and axonal regeneration were also markedly enhanced, which promoted locomotor recovery in the model rats. Collectively, our findings support the conclusion that tau inhibition can attenuate neuroinflammation, alleviate oxidative stress, protect residual cells, facilitate neurogenesis, and improve the functional recovery after spinal cord injury, and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

Key words: functional recovery, MAPK pathway, microglial polarization, neuroinflammation, neuronal regeneration, oxidative stress, spinal cord injury, tau