中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (8): 1387-1393.doi: 10.4103/1673-5374.253523

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

跑台训练改善缺血性卒中大鼠神经损伤及抑制神经细胞凋亡作用的途径

  

  • 出版日期:2019-08-15 发布日期:2019-08-15
  • 基金资助:

    中西医结合治疗脑小血管病临床研究项目（ZHYY-ZXYJHZX-201625）

Treadmill training improves neurological deficits and suppresses neuronal apoptosis in cerebral ischemic stroke rats

Li-Mei Cao, Zhi-Qiang Dong, Qiang Li, Xu Chen   

  1. Department of Neurology, Shanghai No. 8 People’s Hospital, Shanghai, China
  • Online:2019-08-15 Published:2019-08-15
  • Contact: Xu Chen, MD, CXWP65@163.com.
  • Supported by:

    This study was supported by Clinical Study on Treatment of Cerebral Small Blood Vessel Disease by Integrated Traditional Chinese and Western Medicine of China, No. ZHYY-ZXYJHZX-201625 (to LMC).

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摘要：

康复训练被认为对卒中患者的康复有益，然而其分子机制尚不明确。实验以大脑中动脉闭塞/再灌注建立脑缺血性卒中大鼠模型，然后以不同强度跑台康复训练，30min/次，2次/d，进行康复训练。其中低训练强度为5 m/min运动10min，休息10min，跑圈10min；中训练强度为5min内逐渐从5 m/min增加到10 m/min，继续以10 m/min运动5min，休息10min，跑圈10min；高训练强度为5min内逐渐从5 m/min增加到25 m/min，继续以25m/min运动5min，休息10min，跑圈10min。以Bederson量表评价运动功能改善情况，以TTC染色检测脑梗死体积，以TUNEL染色检测脑组织中神经细胞的凋亡，以Western blot分析大鼠脑组织中cAMP/蛋白激酶A和Akt/糖原合成酶激酶3β信号通路的活化情况。结果显示：(1)不同强度的训练均能降低脑卒中大鼠的神经功能缺损评分，减小脑梗死体积，减少脑组织中神经细胞的凋亡；(2)活化cAMP/蛋白激酶A和Akt/糖原合成酶激酶3β信号通路，且运动强度越大，效果越明显；(3)以侧脑室注射蛋白激酶A抑制剂Rp-cAMP预处理大鼠则会抑制上述变化；(4)数据表明康复训练保护神经作用是通过激活cAMP/蛋白激酶A及Akt/糖原合成酶激酶3β信号通路实现的。

orcid: 0000-0003-2181-8306 (Xu Chen)

关键词: 缺血性卒中, 跑台训练, 神经元缺陷, cAMP, 蛋白激酶A, Akt, 糖原合成酶激酶3&beta, 神经保护, 神经再生

Abstract:

Rehabilitation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of ce¬rebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intensities, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3β signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways.

Key words: nerve regeneration, ischemic stroke, treadmill training, neuronal deficit, apoptosis, cyclic adenosine monophosphate, protein kinase A, glycogen synthase kinase-3β, neuroprotective effect, neural regeneration