中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (18): 1678-1687.doi: 10.4103/1673-5374.141802

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

人参皂甙Rd抑制脊髓缺血再灌注损伤后神经元的凋亡

  

  • 收稿日期:2014-08-22 出版日期:2014-09-26 发布日期:2014-09-26
  • 基金资助:

    吉林省科技发展计划项目(20110915)

Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury

Baogang Wang 1, Qingsan Zhu 2, Xiaxia Man 3, Li Guo 4, Liming Hao 5   

  1. 1 Department of Cardiac Surgery, First Hospital of Jilin University, Changchun, Jilin Province, China
    2 Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
    3 Department of Oncological Gynecology, First Hospital of Jilin University, Changchun, Jilin Province, China
    4 Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China
    5 Department of Histology and Embryology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province, China
  • Received:2014-08-22 Online:2014-09-26 Published:2014-09-26
  • Contact: Qingsan Zhu, Ph.D., Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China, drzqs@yahoo.com.cn.
  • Supported by:

    This study was financially supported by a grant from the Jilin Provincial Science and Technology Development Program Foundation of China, No. 20110915.

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摘要：

人参皂甙Rd对缺血性脑卒中有明确的神经保护作用。实验希望验证对于同样属于中枢神经系统的脊髓组织发生缺损再灌注损伤时，Rd可同样起神经保护作用，具有相似的抗神经元凋亡机制。实验以夹闭大鼠肾动脉水平以下腹主动脉1 h，建立脊髓缺血再灌注损伤大鼠模型，以6.25，12.5，25，50 mg/kg•d剂量腹腔注射人参皂甙Rd，分别于缺血再灌注损伤后第1，3，5，7天进行脊髓组织的形态学检测。发现腹腔注射Rd的缺血再灌注损伤模型大鼠后肢运动功能及脊髓前角运动神经元形态均有改善，神经元凋亡明显减轻。Rd的最佳作用剂量确定为25 mg/kg•d，最佳作用时间确定为缺血再灌注损伤后第5天。免疫组织化学染色和Western blot检测显示，Rd可以剂量依赖方式抑制缺血再灌注损伤大鼠脊髓组织中促凋亡蛋白-Caspase3的表达，并下调脊髓组织中ASK1、JNK、P38MAPK蛋白的表达。结果表明人参皂甙Rd对脊髓缺血再灌注损伤起神经保护作用，其潜在机制在于通过抑制ASK1-JNK途径最终抑制caspase3的表达而实现的。

关键词: 神经再生, 脊髓损伤, 神经元, 人参皂甙Rd, 缺血再灌注损伤, 继发性损伤, 凋亡, ASK1, JNK, P38MAPK, caspase3

Abstract:

Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-dependently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reperfusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

Key words: nerve regeneration, spinal cord injury, ginsenoside Rd, ischemia/reperfusion injury, apoptosis, ASK1, JNK, Caspase 3, neural regeneration