中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (2): 283-289.doi: 10.4103/1673-5374.199006

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

依达拉奉通过抑制整合应激反应减缓氧葡萄糖血清剥夺/再灌注引起的脊髓星形胶质细胞凋亡

  

  • 收稿日期:2017-01-25 出版日期:2017-02-15 发布日期:2017-02-15
  • 基金资助:

    广州市科技项目（CJ20130029）

Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

Bin Dai1, 2, Ting Yan3, Yi-xing Shen1, You-jia Xu1, Hai-bin Shen2, Dong Chen2, Jin-rong Wang2, Shuang-hua He4, Qi-rong Dong1, Ai-liang Zhang4   

  1. 1 Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; 
    2 Department of Orthopedics, Binhai County People’s Hospital, Binhai, Jiangsu Province, China; 
    3 Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China; 
    4 Department of Orthopedics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
  • Received:2017-01-25 Online:2017-02-15 Published:2017-02-15
  • Contact: Qi-rong Dong or Ai-liang Zhang,dqrsdefy@163.com or ailiangzhang07@163.com.
  • Supported by:

    This work was supported by a grant from the Science & Technology Bureau of Changzhou City of China, No. CJ20130029.

PDF

713

摘要：

 

课题组以往研究发现，氧葡萄糖血清剥夺/再灌注损伤可诱导PERK/eIF2α/ATF4整合应激反应和caspase-12细胞凋亡途径，进而引起脊髓星形胶质细胞的凋亡。我们假设，/再灌注引起的脊髓星形胶质细胞凋亡。实验设计了8 h/再灌注6 h损伤大鼠原代星型胶质细胞模型，并采用依达拉奉0.1，1，10，100 μM干预培养。发现100 μM可显著抑制氧葡萄糖血清剥夺8 h/再灌注6 h引起的脊髓星形胶质细胞凋亡、活性氧释放、C/EBP同源蛋白（CHOP）表达、caspase-12和caspase-3的活化、PERK和eIF2α的磷酸化及ATF4蛋白的表达。说明依达拉奉通过抑制整合应激反应，能够产生减少氧葡萄糖血清剥夺/再灌注引起的脊髓星形胶质细胞凋亡的作用。依达拉奉葡萄糖血清剥夺低分子氧自由基清除剂依达拉奉通过抑制整合应激反应减缓氧葡萄糖血清剥夺

 

ORCID:0000-0003-2916-5792(Qi-rong Dong)

关键词: 神经再生, 脊髓损伤, 依达拉奉, 凋亡, 星形胶质细胞, 整合应激反应, ROS , PERK , eIF2α, ATF4 , CHOP , caspase-3 , caspase-12

Abstract:

We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM) treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

Key words: nerve regeneration, edaravone, apoptosis, astrocytes, integrated stress response, reactive oxygen species, PERK, eIF2α, activating transcription factor 4, CCAAT/enhancer binding protein homologous protein, caspase-3, caspase-12, neural regeneration