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 (3): 409-416.doi: 10.4103/1673-5374.202944

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

电针干预3 d脑缺血再灌注大鼠海马区细胞凋亡指数下降并抑制p38MAPK的表达

  

  • 收稿日期:2016-12-25 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    国家自然科学基金（81173355）

Electroacupuncture reduces apoptotic index and inhibits p38 mitogen-activated protein kinase signaling pathway in the hippocampus of rats with cerebral ischemia/reperfusion injury

Xiao Lan1, Xin Zhang2, Guo-ping Zhou1, Chun-xiao Wu1, Chun Li2, Xiu-hong Xu1   

  1. 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China; 2 College of Acupuncture, Moxibustion and Tuina, Hunan University of Chinese Medicine, Changsha, Hunan Province, China
  • Received:2016-12-25 Online:2017-03-15 Published:2017-03-15
  • Contact: Guo-ping Zhou, M.D.,doctorzgp@sina.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81173355.

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摘要：

电针可减轻脑缺血再灌注损伤导致的脑组织缺氧及神经细胞凋亡，为进一步明确其机制，我们假设电针修复脑缺血再灌注损伤与细胞凋亡信号传导中的p38MAPK信号通路有关。实验采用改良Zea Longa法建立脑缺血再灌注大鼠模型，于建模前30 min在大脑左侧侧脑室单独注射 p38MAPK阻滞剂SB，于造模后1.5 h在大鼠患侧单独电针尺泽 (LU5)、合谷”(LI4)、足三里(ST36)、三阴交(SP6)穴20 min。当以两种方法联合干预后发现，各组大鼠神经功能缺损评分均明显降低，但各组间无明显差异；苏木精-伊红染色显示各组大鼠脑组织细胞损伤程度均减轻，联合组与SB阻滞剂组相比，细胞排列较整齐，结构较完整，存活神经元较多；TUNEL法检测显示，各组大鼠脑组织细胞凋亡指数均下降，与SB阻滞剂组比较，联合组在再灌注1 d脑组织细胞凋亡指数下降较明显；免疫组织化学染色显示，与模型组比较，电针组和联合组在再灌注3 d时脑组织p-p38表达下降，但SB阻滞剂组无显著差异。结果可证实，电针减轻脑缺血/再灌注损伤的作用途径可能与抑制p38MAPK信号通路的表达有关，连续治疗3 d可能延长促进脑缺血神经修复的治疗时间窗。

ORCID:0000-0002-4613-4384(Guo-ping Zhou)

关键词: 神经再生, 脑损伤, 针刺, 电针, 细胞凋亡, 神经细胞凋亡, 脑缺血再灌注, 神经功能缺损评分, 细胞形态学, 免疫组织化学染色, p38MAPK, p-p38, 海马

Abstract:

Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury. To further identify the involved mechanisms, we assumed that electroacupuncture used to treat cerebral ischemia/reperfusion injury was associated with the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We established rat models of cerebral ischemia/reperfusion injury using the modified Zea-Longa’s method. At 30 minutes before model establishment, p38 MAPK blocker SB20358 was injected into the left lateral ventricles. At 1.5 hours after model establishment, electroacupuncture was administered at acupoints of Chize (LU5), Hegu (LI4), Zusanli (ST36), and Sanyinjiao (SP6) for 20 minutes in the affected side. Results showed that the combination of EA and SB20358 injection significantly decreased neurologic impairment scores, but no significant differences were determined among different interventional groups. Hematoxylin-eosin staining also showed reduced brain tissue injuries. Compared with the SB20358 group, the cells were regularly arranged, the structures were complete, and the number of viable neurons was higher in the SB20358 + electroacupuncture group. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling assay showed a decreased apoptotic index in each group, with a significant decrease in the SB20358 + electroacupuncture group. Immunohistochemistry revealed reduced phosphorylated p38 expression at 3 days in the electroacupuncture group and SB20358 + electroacupuncture group compared with the ischemia/reperfusion group. There was no significant difference in phosphorylated p38 expression between the ischemia/reperfusion group and SB20358 group. These findings confirmed that the electroacupuncture effects on mitigating cerebral ischemia/reperfusion injury are possibly associated with the p38 MAPK signaling pathway. A time period of 3 days could promote the repair of ischemic cerebral nerves.

Key words: nerve regeneration, brain injury, electroacupuncture, cell apoptosis, cerebral ischemia/reperfusion injury, neurological impairment score, morphological changes, immunohistochemical assay, p38 mitogen-activated protein kinases, phosphorylated p38, hippocampus, neural regeneration