天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (9): 988-991.doi: 10.11958/j.issn.0253-9896.2015.09.008

• 实验研究 • 上一篇    下一篇

依达拉奉抗大鼠脊髓损伤后脊髓细胞凋亡的机制初探

王继权， 赵兴长， 孙平， 李昊天， 褚鑫， 吕刚， 范仲凯△   

  1. 辽宁锦州， 辽宁省辽宁医学院附属第一医院骨科 （邮编121001）
  • 收稿日期:2015-01-29 修回日期:2015-05-12 出版日期:2015-09-15 发布日期:2015-09-15
  • 通讯作者: 范仲凯 E-mail: flanzz@163.com E-mail:wangjiquan1989@163.com
  • 作者简介:王继权 （1989）， 男， 硕士在读， 主要从事脊髓损伤的机制及修复研究
  • 基金资助:
    国家自然科学基金资助项目 （81272074）； 辽宁省高等学校优秀人才支持计划项目 （LJQ2014091）； 辽宁医学院校长基金项目（QM2014011）

Preliminary mechanism of edaravone against cell apoptosis after spinal cord injury in rats

WANG Jiquan, ZHAO Xingchang, SUN Ping, LI Haotian, CHU Xin, LYU Gang, FAN Zhongkai △   

  1. First Affiliated Hospital of Liaoning Medical College, Jinzhou 121001, China
  • Received:2015-01-29 Revised:2015-05-12 Published:2015-09-15 Online:2015-09-15
  • Contact: △Corresponding Author E-mail: flanzz@163.com E-mail:wangjiquan1989@163.com

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摘要： 摘要： 目的 探讨依达拉奉 （EDA） 对大鼠脊髓损伤 （SCI） 后内质网应激 （ERS） 介导的细胞凋亡的影响。方法 36 只 SD 大鼠随机分为假手术(sham)组、 SCI 组、 EDA 组， 每组 12 只。采用 Allen’ s 法建立 SCI 模型， sham 组仅行椎板切除术。术后 Sham 组和 SCI 组给予与 EDA 组等体积等频次生理盐水处理； EDA 组在 SCI 模型建成以后予以 EDA(10 mg/kg)， 每 12 h 腹腔注射给药 1 次。于术后 3 d 取脊髓， 应用 Western blot 检测 C/EBP 同源蛋白 （CHOP）、 Cleaved caspase-12 和 Cleaved caspase-3 的表达水平， 免疫荧光技术检测脊髓组织中 caspase-12、 CHOP 阳性细胞的比率， TUNEL 法检测脊髓细胞凋亡水平。结果 SCI 组较 sham 组 CHOP、 Cleaved caspase-12、 Cleaved caspase-3 的表达升高， Cleaved caspase-12、 CHOP 阳性细胞比率增加， 脊髓组织细胞凋亡比率增加 （均 P < 0.01）。EDA 组较 SCI 组 CHOP、 Cleaved caspase-12 和 Cleaved caspase-3 的表达降低， Cleaved caspase-12、 CHOP 阳性细胞比率减少， 脊髓组织细胞凋亡比率减少 （均 P < 0.01）。结论 EDA 对脊髓损伤有保护作用， 机制可能与其抑制 SCI 后脊髓细胞的 ERS 和脊髓细胞的凋亡有关。

关键词: 脊髓损伤, 细胞凋亡, 半胱氨酸天冬氨酸蛋白酶 , 半胱氨酸天冬氨酸蛋白酶 , 模型, 动物, 大鼠, Sprague-Dawley, 内质网应激, 依达拉奉, 转录因子 CHOP

Abstract: Abstract: Objective To investigate the effects of edaravone (EDA) on cell apoptosis induced by endoplasmic reticu⁃ lum stress (ESR) after spinal cord injury (SCI) in rats. Methods Thirty-six healthy adult SD rats were randomly divided in⁃ to three groups (12 rats for each group): Sham group, SCI group and EDA group. The rat model of SCI was made by Allen’ s method and the sham group was only received laminectomy and kept the spinal cord intact. Rats in sham group and SCI group accepted the same volume and frequency of saline injection as EDA group. The EDA group was given 10 mg/kg EDA once every 12 h intraperitoneally. Three days after injuring, the spinal cords were harvested, and the protein levels of C/EBP homologous protein (CHOP), Cleaved caspase-12 and Cleaved caspase-3 were detected by Western blot assay. Immunofluo⁃ rescence staining was used to analyze the positive ratio of caspase-12 and CHOP in spinal cord of three groups. Meanwhile, TUNEL staining was used to identify cell apoptosis of spinal cord. Results Compared with sham group, the protein levels of CHOP, Cleaved caspase-12 and Cleaved caspase-3 were obviously higher in SCI group (P < 0.01); the proportion of Cas⁃ pase-12 and CHOP positive cells was significantly increased (P < 0.01), and the apoptotic rates were also significantly in⁃ creased in spinal cord (P < 0.01). However, compared with SCI group, the protein levels of CHOP , Cleaved caspase-12 and Cleaved caspase-3 were significantly decreased in EDA group (P < 0.01); the proportion of Caspase-12 and CHOP positive cells was significantly reduced (P < 0.01), and the apoptotic rates were also significantly decreased in spinal cord (P < 0.01). Conclusion EDA has neuroprotective potential to spinal cord injury. The mechanism of its neuroprotective effect may asso⁃ ciate with its inhibitory effect to the cell apoptosis induced by endoplasmic reticulum stress after SCI.

Key words: spinal cord injury, apoptosis, caspase 3, caspase 12, models, animal, rats, Sprague-Dawley, endoplasmic reticulum stress, edaravone, transcription factor CHOP