中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (7): 1578-1583.doi: 10.4103/1673-5374.357904

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

抑制磷酸酶肌动蛋白调节因子1表达对创伤性脑损伤的神经保护

  

  • 出版日期:2023-07-15 发布日期:2023-01-12
  • 基金资助:
    国家自然科学基金项目(81501048,81801236,81974189);上海市第六人民医院研究基金项目(ynlc201808)

Inhibiting phosphatase and actin regulator 1 expression is neuroprotective in the context of traumatic brain injury

Yao Jing#, Lin Zhang#, Shi-Wen Chen#, Yan Guo, Shi-Ming Ju, Fang Yuan, Hao Chen, Dian-Xu Yang, Heng-Li Tian*, Zhi-Ming Xu*, Jun Ding* #br#   

  1. Department of Neurosurgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Online:2023-07-15 Published:2023-01-12
  • Contact: Jun Ding, MD, PhD, djdjdoc@126.com; Zhi-Ming Xu, MD, PhD, zhiming0369@163.com; Heng-Li Tian, MD, PhD, tianhlsh@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81501048 (to JD), 81801236 (to ZMX), 81974189 (to HLT); and Shanghai 6th People’s Hospital Research Fund, No. ynlc201808 (to JD).

摘要:

有研究发现,磷酸酶肌动蛋白调节因子1表达升高可诱导蛛网膜下腔出血和脑卒中的发生,但在创伤性脑损伤后磷酸酶肌动蛋白调节因子1的表达变化和作用尚不清楚。因此实验做了如下的观察:(1)以受控皮质冲击建立创伤性脑损伤小鼠模型,证实其脑组织中磷酸酶肌动蛋白调节因子1蛋白表达增加,且定位于内皮细胞、神经元、星形胶质细胞和小胶质细胞中。(2)以携带PHACTR-1小发夹RNA的腺相关病毒载体转染创伤性脑损伤小鼠模型,可见小鼠脑组织含水量增加。而敲低磷酸酶肌动蛋白调节因子1蛋白后,脑组织含水量减少。(3)最后还发现抑制磷酸酶肌动蛋白调节因子1蛋白表达可通过调控核因子κB信号通路,降低血脑屏障通透性以及水通道蛋白4和细胞间黏附分子1的表达,抑制星形胶质细胞和小胶质细胞相关的神经炎症以及神经细胞的凋亡,从而改善神经功能。(4)实验结果提示磷酸酶肌动蛋白调节因子1在治疗创伤性脑损伤动物模型水平上具有潜在治疗靶点的作用。

https://orcid.org/0000-0001-5931-992X (Jun Ding); 

https://orcid.org/0000-0001-5490-9517 (Zhi-Ming Xu);

https://orcid.org/0000-0003-0525-503X (Heng-Li Tian)

关键词: 磷酸酶肌动蛋白调节因子1, 血脑屏障, ZO-1, Occludin, 水通道蛋白 4, 细胞间粘附分子1, 神经炎症, 细胞凋亡, 核因子κB, 创伤性脑损伤

Abstract: Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke, but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury. In this study we found that, in a mouse model of traumatic brain injury induced by controlled cortical impact, phosphatase actin regulatory factor 1 expression is increased in endothelial cells, neurons, astrocytes, and microglia. When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice, the water content of the brain tissue increased. However, when phosphatase actin regulatory factor 1 was knocked down, the water content decreased. We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway, decreased blood-brain barrier permeability, reduced aquaporin 4 and intercellular adhesion molecule 1 expression, inhibited neuroinflammation, and neuronal apoptosis, thereby improving neurological function. The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury. 

Key words: apoptosis, aquaporin 4, blood brain barrier, intercellular adhesion molecule 1, neuroinflammation, nuclear factor kappa B, occludin, phosphatase and actin regulator-1, traumatic brain injury, zonula occludens 1