中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (9): 1536-1543.doi: 10.4103/1673-5374.255973

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

水芹提取物预处理可保护短暂性缺血后损伤的海马神经元

  

  • 出版日期:2019-09-15 发布日期:2019-09-15
  • 基金资助:

    该研究由基础科学研究计划通过由教育部资助的韩国国家研究基金会(NRF)(NRF-2017R1D1A1B03033271,JDK)以及国家研究基金会科学,ICT和未来规划部生物协同研究项目(NRF-2018M3A9C4076478,IJK)提供资助

Pretreated Oenanthe Javanica extract increases anti-inflammatory cytokines, attenuates gliosis, and protects hippocampal neurons following transient global cerebral ischemia in gerbils

Joon Ha Park 1 , In Hye Kim 2 , Ji Hyeon Ahn 1 , YooHun Noh 2 , Sung-Su Kim 2 , Tae-Kyeong Lee 3 , Jae-Chul Lee 3 , Bich-Na Shin 4 , Tae Heung Sim 4 , Hyun Sam Lee 4 , Jeong Hwi Cho 5 , In Koo Hwang 6 , Il Jun Kang 7 , Jong Dai Kim 8 , Moo-Ho Won 3   

  1. 1 Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon, Republic of Korea
    2 Famenity Company, Gwacheon, Geyonggi, Republic of Korea
    3 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
    4 Danchunok Company, Chuncheon, Gangwon, Republic of Korea
    5 Department of Histology, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeollabuk?do, Republic of Korea
    6 Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea
    7 Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon, Republic of Korea
    8 Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Moo-Ho Won, DVM, PhD, mhwon@kangwon.ac.kr; Jong Dai Kim, PhD, jongdai@kangwon.ac.kr.
  • Supported by:

    This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03033271, to JDK), and by the Bio-Synergy Research Project (NRF-2018M3A9C4076478, to IJK) of the Ministry of Science, ICT and Future Planning through the National Research Foundation.

摘要:

已有研究显示水芹提取物对短暂性全脑缺血有神经保护作用;然而,水芹提取物的神经保护作用机制尚未完全明确。因此,实验在沙鼠5min短暂性全脑缺血前每天一次以100和200mg/kg剂量灌胃水芹提取物,持续1周。(1)实验以神经元核抗原免疫组化染色和Fluoro-Jade B的组织荧光染色观察水芹提取物对神经元的神经保护。以胶质纤维酸性蛋白和离子化钙结合衔接分子1的免疫组化染色观察星形胶质细胞增生和小神经胶质细胞增生情况,以肿瘤坏死因子α和白细胞介素2免疫组织化学染色检测水芹提取物促炎功能,以白细胞介素4和白细胞介素13免疫组织化学染色检测水芹提取物抗炎功能;(2)结果发现,200mg/kg水芹提取物预处理可保护海马CA1区锥体神经元免于短暂性全脑缺血损伤,并抑制脑缺血诱导的神经胶质增生。同时发现水芹提取物预处理使缺血CA1区锥体神经元的白细胞介素4和白细胞介素13免疫反应性明显增加。结果表明,水芹提取物预处理可以通过增加白细胞介素4和白细胞介素13的表达来保护短暂性全脑缺血后的神经元损伤,减弱神经胶质增生。

orcid: 0000-0002-7178-6501 (Moo-Ho Won)
           0000-0002-3694-7816 (Jong Dai Kim)

关键词: 水芹提取物, 短暂性全脑缺血, 海马, 缺血性损伤, 脑缺血, 神经保护, 胶质细胞活化, 促炎细胞因子, 抗炎细胞因子, 炎症

Abstract:

Recently, we have reported that Oenanthe javanica extract (OJE) displays strong neuroprotective effect      against ischemic damage after transient global cerebral ischemia. However, neuroprotective mechanisms of OJE have not been fully identified. Thus, this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia. We treated the animals by intragastrical injection of OJE (100 and 200 mg/kg) once daily for 1 week prior to transient global cerebral ischemia. Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B. Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis, respectively. To investigate the neuroprotective mechanisms of OJE, we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function. When we treated the animals by intragastrical administration of 200 mg/kg of OJE, hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area. We also found that interleukin-4 and -13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment, and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia. However, OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons. Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and -13. The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) in Kangwon National University (approval No. KW-160802-1) on August 10, 2016.

Key words: Oenanthe javanica extract, transient global cerebral ischemia, hippocampus, ischemic damage, cerebral ischemia, neuroprotection, glial activation, pro-inflammatory cytokines, anti-inflammatory cytokines, inflammation, neural regeneration