中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 1080-1087.doi: 10.4103/1673-5374.324857

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

黄芩苷改善脊髓损伤的机制

  

  • 出版日期:2022-05-15 发布日期:2021-11-22

Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury

Rui Zhao1, 2, 3, #, Xue Wu1, 2, 3, #, Xue-Yuan Bi4, Hao Yang1, 3, Qian Zhang1, 2, 3, *   

  1. 1College of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, Shaanxi Province, China; 2Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi Province, China; 3Translational Medicine Center, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China; 4Department of Pharmacy, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
  • Online:2022-05-15 Published:2021-11-22
  • Contact: Qian Zhang, PhD, zq-melody@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81403278; the Natural Science Foundation of Shaanxi Province of China, No. 2017JM8058; and the Fundamental Research Funds for the Central Universities of China, No. GK202103079 (all to QZ).

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摘要：

黄芩苷是从传统中药黄芩中提取的一种天然活性成分，可穿越血脑屏障，对多种中枢神经系统疾病提供神经保护作用，但其对脊髓损伤（SCI）的保护机制仍不清楚。（1）实验首先以改良的Allen打击法建立脊髓损伤模型，以腹腔注射黄芩苷进行干预。结果显示，黄芩苷可显著提高BBB评分，降低血-脊髓屏障的通透性，减少损伤脊髓中Bax，Caspase-3，核因子κB表达，并增加Bcl-2表达，同时逆转脊髓病理损伤，并减少神经元的凋亡；（2）进一步以10 mM谷氨酸诱导12h构建了SH-SY5Y细胞兴奋毒性模型，并以40μM黄芩苷干预48h进行治疗以检验黄芩苷的作用机制。结果发现，黄芩苷能逆转紧密蛋白occludin和ZO-1以及凋亡相关蛋白Bax，Bcl-2，Caspase-3和核因子κB的表达趋势，并上调PI3K以及Akt的磷酸化。且上述作用可被PI3K抑制剂LY294002预处理所抑制；（3）提示黄芩苷可抑制脊髓损伤后血-脊髓屏障通透性，并减少神经元凋亡，其作用机制与激活PI3K/Akt信号通路有关。实验于2014年3月6日经西安交通大学动物伦理委员会批准（批准号SCXK [陕] 2007-001）。

https://orcid.org/0000-0002-3859-6503 (Qian Zhang)

关键词: 黄芩苷, 天然药物, 脊髓损伤, 血-脊髓屏障, 紧密连接蛋白, 神经元, 细胞凋亡, PI3K/Akt信号通路

Abstract: Baicalin  is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen’s impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 µM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi’an Jiaotong University on March 6, 2014. 

Key words: apoptosis, baicalin, blood-spinal cord barrier, natural products, neuron, PI3K/Akt signaling pathway, spinal cord injury, tight junction 

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