中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 78-85.doi: 10.4103/1673-5374.264465

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

毛冬青甲素促进局灶性脑缺血后海马CA1区星形胶质细胞和小胶质细胞的活化

  

  • 出版日期:2020-01-15 发布日期:2020-05-20
  • 基金资助:

    福建省自然科学基金（2014J01327）；福建省高校新世纪优秀人才培养计划（NCETFJ-0704）；福建医科大学教授学术发展基金（JS09014）

Characterization of astrocytes and microglial cells in the hippocampal CA1 region after transient focal cerebral ischemia in rats treated with Ilexonin A

Ai-Ling Xu1, 2, Guan-Yi Zheng1, Hui-Ying Ye1, 3, Xiao-Dong Chen4, Qiong Jiang4   

  1. 1 Department of Traditional Chinese Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
    2 Department of Neonatology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
    3 Department of Neurology, People’s Hospital of Nanping, Nanping, Fujian Province, China
    4 Burns Institute of Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
  • Online:2020-01-15 Published:2020-05-20
  • Contact: Guan-Yi Zheng, PhD, drzhenggy@126.com.
  • Supported by:
    This study was supported by the Natural Science Foundation of Fujian Province of China, No. 2014J01327; the Program for New Century Excellent Talents in Colleges and Universities of Fujian Province of China, No. NCETFJ-0704; the Professorial Academic Development Foundation of Fujian Medical University of China, No. JS09014 (all to GYZ).

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摘要：

毛冬青甲素是一种从中国中药毛冬青根部分离出来的化合物，既往研究显示其能通过调节缺血后梗死周围区域星形胶质细胞和小胶质细胞的活化，发挥神经保护作用，但其对于无梗死区域大脑海马CA1区星形胶质细胞和小胶质细胞的作用尚不明确。实验通过闭塞大鼠大脑中动脉血管2h建立局灶性脑缺血模型，分别在缺血再灌注后立即腹腔注射20，40，80mg/kg毛冬青甲素。(1)以免疫组化和Western blot检测海马CA1区星形胶质细胞标志物胶质纤维酸性蛋白、小胶质细胞标志物Iba-1以及神经干细胞标志物Nestin的阳性细胞数量以及表达水平，以ELISA检测海马CA1区炎症标志物肿瘤坏死因子α和白细胞介素1β的表达水平；(2)结果见局灶性脑缺血后1-7d时海马CA1区星形胶质细胞数量逐渐增加，而经毛冬青甲素治疗的大鼠海马CA1区星形胶质细胞数量进一步增加；小胶质细胞在局灶性脑缺血后仍保持静止状态，但经毛冬青甲素干预后可被激活；毛冬青甲素能增强Nestin的表达；并降低局灶性脑缺血后海马中肿瘤坏死因子α和白细胞介素1β的表达；(3)结果表明毛冬青甲素可通过调节星形胶质细胞和小胶质细胞激活，促进神经干细胞增殖和降低促炎因子水平，对局灶性脑缺血海马神经元可发挥神经保护作用。实验于2009-06-06经福建医科大学附属协和医院动物伦理委员会批准。

orcid: 0000-0002-7561-4563 (Guan-Yi Zheng)

关键词:

短暂性局灶性脑缺血, 大脑中动脉闭塞, 海马CA1区, 星形胶质细胞, 小胶质细胞, 神经干细胞, 神经保护, 毛冬青甲素, 神经再生

Abstract: Ilexonin A is a compound isolated from the root of Ilex pubescens, a traditional Chinese medicine. Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia. However, the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear. Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats. Ilexonin A (20, 40 or 80 mg/kg) was administered immediately after ischemia/reperfusion. The astrocyte marker glial fibrillary acidic protein, microglia marker Iba-1, neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay. Expression levels of tumor necrosis factor-α and interleukin 1β were determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue. Astrocytes were activated immediately in progressively increasing numbers from 1, 3, to 7 days post-ischemia/reperfusion. The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A. Microglial cells remained quiescent after ischemia/ reperfusion, but became activated after treatment with ilexonin A. Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-α and interleukin 1β in the hippocampus post-ischemia/reperfusion. The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion, probably through regulating astrocytes and microglia activation, promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors. This study was approved by the Animal Ethics Committee of the Fujian Medical University Union Hospital, China.

Key words: astrocytes, hippocampal CA1 region, ilexonin A, microglia, middle cerebral artery occlusion, neural stem cell, neuroprotection,
transient focal cerebral ischemia

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