中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (11): 1830-1835.doi: 10.4103/1673-5374.170313

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

丝氨酸苏氨酸蛋白激酶活化可成为减少脊髓损伤后神经元凋亡的有效靶点?

  

  • 收稿日期:2015-08-31 出版日期:2015-12-07 发布日期:2015-12-07
  • 基金资助:

    中国国家自然科学基金项目(81271387),国家卫生和计划生育委员会专项基金(201402009),国家重大科技项目(Z141107002514031)

Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury

Mu Jin#, Yan-wei Yang#, Wei-ping Cheng*, Jia-kai Lu*, Si-yu Hou, Xiu-hua Dong, Shi-yao Li   

  1. Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
  • Received:2015-08-31 Online:2015-12-07 Published:2015-12-07
  • Contact: Wei-ping Cheng, M.D. or Jia-kai Lu, M.D., ch_eng9735@sina.com.cn or lujiakai620@163.com.
  • Supported by:

    This research was supported by the National Natural Science Foundation of China, No. 81271387; the Research Special Fund of Public Welfare and Health Department of China, No. 201402009; the National Key Technology R&D Program in China, No. Z141107002514031.

摘要:

为验证脊髓缺血后与细胞凋亡有关的信号转导通路主要包括细胞外信号调节激酶和丝氨酸苏氨酸蛋白激酶信号通路及c-Jun氨基末端激酶为促进细胞凋亡信号通路的作用。实验采用球囊压迫左锁骨下动脉25min建立急性脊髓损伤大鼠模型,模型大鼠出现后肢功能明显障碍,脊髓组织中神经元损害的病理变化,脊髓前角和中央管有较多凋亡细胞,损伤后48h时凋亡细胞数量最多。再灌注后即刻脊髓组织中磷酸化丝氨酸苏氨酸蛋白激酶和磷酸化细胞外信号调节激酶明显升高,且随着时间的延长而增加,再灌注后4或2h达峰值,12 h时下降,24 h时再次抬升。脊髓组织中磷酸化c-Jun氨基末端激酶表达在再灌注后降低,12 h时增加至接近正常水平,24h后又呈下降趋势。我们以Pearson线性相关分析也显示出细胞凋亡数量与磷酸化丝氨酸苏氨酸蛋白激酶表达水平呈负相关。表明缺血再灌注阶段丝氨酸苏氨酸蛋白激酶的活化是脊髓缺血后神经元凋亡延迟的重要因素。以此推论,可否使之成为减少脊髓损伤后神经元凋亡的保护靶点?

关键词: 神经再生, 缺血性脊髓损伤, 细胞凋亡, 神经功能, 丝氨酸苏氨酸蛋白激酶, 细胞外信号调节激酶, c-Jun氨基末端激酶

Abstract:

The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.

Key words: nerve regeneration, ischemic spinal cord injury, apoptosis, neurological function, serine-threonine protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, neural regeneration