中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (3): 445-450.doi: 10.4103/1673-5374.153694

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

中药复方制剂通络救脑注射液保护脑缺血的途径:活化神经营养因子3/原肌球蛋白相关激酶通路

  

  • 收稿日期:2015-01-06 出版日期:2015-03-20 发布日期:2015-03-20
  • 基金资助:

    973课题(2012CB518602);国家自然科学基金(30830120);北京中医药大学课题

Chinese herbal formula Tongluo Jiunao injection protects against cerebral ischemia by activating neurotrophin 3/tropomyosin-related kinase C pathway

Peiman Alesheikh 1, Arezou Mashoufi 1, Hui-ling Tang 2, Wei Zhang 2, Bo Di 2, Yang-yang Yan 2, Peng-tao Li 3, Yan-shu Pan 2   

  1. 1 Research Center of Natural Product Health, North Khorasan University of Medical Science, Bojnourd, North Khorasan, Iran
    2 Department of Pathology, Preclinical Medical School, Beijing University of Chinese Medicine, Beijing, China
    3 Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
  • Received:2015-01-06 Online:2015-03-20 Published:2015-03-20
  • Contact: Yan-shu Pan, Ph.D., arezoopayman@yahoo.com
  • Supported by:

     This work was supported by grants from the National Basic Research Program (973 Program), No. 2012CB518602, the National Natural Science Foundation of China, No. 30830120, and a grant from Beijing University of Chinese Medicine in China.

摘要:

以三七总皂苷、栀子苷为主要成分的中药复方通络救脑注射液已获得专利并在临床应用,虽已被证实对脑缺血有保护作用,但作用途径尚不明确。实验给予大脑中动脉阻塞的脑缺血大鼠模型腹腔注射通络救脑注射液,并与腹腔注射阳性对照药血塞通的大脑中动脉阻塞大鼠模型为对照,探讨通络救脑对脑缺血的神经保护作用途径。结果发现通络救脑干预使大脑中动脉阻塞大鼠模型脑梗死体积明显缩小。酶联免疫吸附分析结果显示,通络救脑液射液干预使大鼠缺血脑组织神经营养因子3和生长相关蛋白43表达明显升高,且前者的血清值也明显升高。反转录聚合酶链反应和免疫组化检测显示,通络救脑注射液使大鼠缺血脑组织神经生长因子受体--原肌球蛋白相关激酶C基因表达和免疫反应明显升高/增强,且通络救脑注射液的上述作用均优于血塞通。说明通络救脑通过活化神经营养因子3/原肌球蛋白相关激酶通路,对脑缺血大鼠模型起到了神经保护作用。

关键词: 神经再生, 脑缺血, 中药复方, 通络救脑注射液, 神经生长因子受体, 神经营养因子, 血塞通, 神经保护

Abstract:

The Chinese herbal formula Tongluo Jiunao, containing the active components Panax notoginseng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control (Xuesai Tong, containing Panax notoginseng) or saline intraperitoneally to investigate the pathway involved in the action of Tongluo Jiunao injection. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo Jiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo Jiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/tropomyosin-related kinase C pathway.

Key words: neural regeneration, cerebral ischemia, Chinese herbal formula, Tneurotrophic factor, ongluo Jiunao injection, nerve growth factor receptor, Xuesai Tong, neuroprotection, NSFC grant, neuroprotection, neural regeneration