中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (34): 3203-3215.doi: 10.3969/j.issn.1673-5374.2013.34.004

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

葛根素激活胆碱能抗炎通路抗脑缺血再灌注后炎症反应实验研究

  

  • 收稿日期:2013-08-24 修回日期:2013-10-29 出版日期:2013-12-05 发布日期:2013-12-05

Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

Xiaojie Liu, Zhigang Mei, Jingping Qian, Yongbao Zeng, Mingzhi Wang   

  1. Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China
  • Received:2013-08-24 Revised:2013-10-29 Online:2013-12-05 Published:2013-12-05
  • Contact: Zhigang Mei, M.D., Associate professor, Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China, meizhigang@gmail.com.
  • About author:Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China Xiaojie Liu, Master.

摘要:

葛根素是从中国草药葛根中提取的一种异黄酮类单体化合物,可抑制神经凋亡,在缺血再灌注大鼠中发挥较好的抗炎作用。胆碱能抗炎通路(CAP)可通过α7烟碱型乙酰胆碱受体(α7nAChR)快速、持续地抑制炎症因子的释放,而减轻或调节炎症反应。实验通过建立大鼠脑缺血再灌注模型,旨在探讨葛根素抗炎保护的胆碱能抗炎通路机制。结果显示,葛根素预给药可缩小脑缺血再灌注模型大鼠脑梗死面积,改善神经功能损伤,抑制缺血脑组织中炎症因子白细胞介素1β、白细胞介素6和肿瘤坏死因子α的水平,上调缺血再灌注大鼠缺血脑组织中α7烟碱型乙酰胆碱受体、Janus激酶2 JAK2、信号转导子和转录激活子3 STAT3 mRNA的表达,下调核因子кBp65 mRNA以及蛋白的表达。更重要的是α7烟碱型乙酰胆碱受体阻断剂α-银环蛇毒(α-BGT)阻断了葛根素的这些作用。上述结果表明,通过激活胆碱能抗炎通路可能是葛根素抑制大鼠脑缺血再灌注炎症反应,发挥脑保护作用的机制之一。

中国神经再生研究(英文版)杂志出版内容重点: 脑损伤;脊髓损伤;周围神经损伤;帕金森;神经影像;神经再生

关键词: 神经再生, 中医药, 葛根素, 脑缺血再灌注, 炎症反应, 胆碱能抗炎通路, α7烟碱型乙酰胆碱受体, 核因子-κB, 蛋白酪氨酸激酶2, 信号转导子与转录激活子3, 基金资助文章

Abstract:

Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral is-chemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi-ated through the activation of the cholinergic anti-inflammatory pathway.

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