中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (8): 1408-1416.doi: 10.4103/1673-5374.235296

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

栝蒌桂枝汤可促进局灶性脑缺血后神经功能的恢复和神经再生

  

  • 收稿日期:2018-02-15 出版日期:2018-08-15 发布日期:2018-08-15
  • 基金资助:

    福建省卫生计生委研究项目（2014-ZQN-JC-32），福建省教委项目（JZ160442），福建省自然科学基金项目（2018J01855），福建省中药临床前研究与质量控制工程技术研究中心项目（2009Y2003）

Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal erebral ischemia/reperfusion

Jing Han1, Ji-Zhou Zhang1, Zhi-Feng Zhong1, Zuan-Fang Li2, Wen-Sheng Pang2, 3, Juan Hu1, 2, Li-Dian Chen2   

  1. 1 Institute of Materia Medica, Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
    2 Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
    3 The Second People’s Hospital of Fujian Province, Fuzhou, Fujian Province, China
  • Received:2018-02-15 Online:2018-08-15 Published:2018-08-15
  • Contact: Juan Hu, Ph.D. or Li-Dian Chen, Ph.D.,huj@fjtcm.edu.cn or lidianchen87@yahoo.com.
  • Supported by:

    This work was supported by a grant from the Research Project of Fujian Provincial Health and Family Planning Commission of China, No. 2014-ZQN-JC-32; a grant from the Project of Fujian Province Office of Education of China, No. JZ160442; the Natural Science Foundation of Fujian Province of China, No. 2018J01855; a grant from the Platform for Preclinical Studies of Traditional Chinese Medicine and Quality Control Engineering Technology Research Center of Fujian Province of China, No. 2009Y2003.

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摘要：

 

神经功能障碍恢复涉及大脑内神经发生和轴突重塑。栝蒌桂枝汤在中国用于治疗卒中后肢体痉挛已有悠久的历史，研究显示其对脑缺血损伤有神经保护作用，但是栝蒌桂枝汤对脑缺血后内源性神经发生和轴突重构的影响仍有待研究。实验通过大脑中动脉闭塞建立局灶性脑缺血再灌注大鼠模型，以Longa的5分评分系统在再灌注后即刻评估神经学行为以确定成功模型，然后将成功建模的大鼠随机分为溶剂组和栝蒌桂枝汤组，并另取行假手术大鼠作为假手术组。栝蒌桂枝汤组大鼠在分组后立即灌胃栝蒌桂枝汤水煎剂，1次/d，连续14d，溶剂组和假手术组灌胃蒸馏水。以平衡木平衡试验评分以及足失误试验观察大鼠行为学变化，以尼氏染色检测脑组织病理变化，以免疫荧光染色检测脑组织中增殖细胞标志物BrdU、神经前体细胞标志物DCX、星形胶质细胞标志物胶质纤维酸性蛋白以及轴突再生标志物生长相关蛋白43的免疫反应。结果发现脑缺血再灌注大鼠经栝蒌桂枝汤水煎剂治疗后，脑组织病理损伤明显减轻，且缺血侧脑室下区BrdU、DCX和胶质纤维酸性蛋白阳性细胞数量增加，梗死周围皮质中的生长相关蛋白43表达增加，且大鼠神经行为能力明显改善。表明栝蒌桂枝汤可通过促进损伤部位细胞增殖，增加神经元前体和星形胶质细胞和梗死周围皮质中的轴突再生，促进神经功能的恢复。

orcid:0000-0003-4747-7503(Juan Hu)
        0000-0002-6776-5855(Li-Dian Chen)
        0000-0002-7142-1991(Jing Han)

关键词: 栝蒌桂枝汤, 细胞增殖, 神经发生, 神经母细胞, 星形胶质细胞, 轴突重塑, 缺血性脑卒中, 中药复方, 神经再生

Abstract:

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction (GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurological function was assessed immediately after reperfusion using Longa’s 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2′-deoxyuridine (BrdU) as well as expression of the neural precursor marker doublecortin (DCX), the astrocyte marker glial fibrillary acidic protein (GFAP) and the axon regeneration marker growth associated protein-43 (GAP-43). GLGZD substantially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and increasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Key words: nerve regeneration, Gualou Guizhi decoction, cell proliferation, neurogenesis, neuroblast, astrocyte, axon remodeling, ischemic stroke, Chinese medicine compound, neural regeneration