主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2019, Vol. 42 ›› Issue (5): 378-388.doi: 10.3969/j.issn.1006-2157.2019.05.005

• 中药药理 • 上一篇    下一篇

复方血栓通胶囊对脑缺血再灌注小鼠神经可塑性的影响*

高文慧, 徐梦, 马青, 杨菲, 陈雪, 张慧明, 唐民科#   

  1. 北京中医药大学中药学院 北京 102488
  • 收稿日期:2018-11-21 出版日期:2019-05-30 发布日期:2019-06-05
  • 通讯作者: 唐民科, 男, 博士, 教授, 博士生导师, 研究方向:神经药理学, E-mail: tangmk@ bucm. edu. cn
  • 作者简介:高文慧,女,在读硕士生
  • 基金资助:
    *国家科技重大专项重大新药创制项目(No.2011ZX 09201-201-22),北京中医药大学研究生自主课题(No.2018-JYB-XS091)

Influence of Fufang Xueshuantong Capsule on neuroplasticity in mice with cerebral ischemia-reperfusion*

Gao Wenhui, Xu Meng, Ma Qing,Yang Fei, Chen Xue, Zhang Huiming, Tang Minke#   

  1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
  • Received:2018-11-21 Online:2019-05-30 Published:2019-06-05
  • Contact: Prof. Tang Minke, Ph. D., Doctoral Supervisor. Beijing University of Chinese Medicine, No. 11, Beishanhuan Donglu Road, Chaoyang District, Beijing 100029. E-mail: tangmk@bucm.edu.cn

摘要: 目的 观察复方血栓通胶囊对脑缺血再灌注损伤小鼠神经可塑性的影响及其相关机制。方法 将雄性脑缺血再灌注小鼠随机分为假手术组,脑缺血再灌注组,复方血栓通胶囊低、中、高剂量组及步长脑心通胶囊组。每组又随机分为1、7、14 d 3个观察时间点,独立成组(n=10)。采用大脑中动脉栓塞法(MCAO)制备模型,假手术组只进行麻醉和血管分离,不进行结扎和栓塞。灌胃给药,每天1次。通过神经功能评分、胶布移除、前肢力量测定实验,评估小鼠神经功能障碍情况;通过监测小鼠死亡率,观察小鼠健康状况。采用尼氏染色和免疫组织化学染色,观察缺血区皮层神经元形态及生长相关蛋白43(GAP-43)、突触素(Syn)表达情况;采用酶联免疫吸附(ELISA)法测定脑组织中神经生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养因子-3(NT-3)含量,观察脑缺血再灌注损伤后神经营养因子水平。结果 与假手术组比较,脑缺血再灌注组小鼠有明显的神经功能缺损及运动功能障碍(P<0.05),死亡率高,缺血区周边组织尼氏体着色变浅,出现空泡,排列稀疏,GAP-43、Syn表达减弱,NGF、BDNF、NT-3含量升高。与脑缺血再灌注组比较,复方血栓通胶囊高、中、低剂量组小鼠神经功能障碍均有恢复,小鼠死亡率降低,尼氏体着色变深、空泡减少、排列更紧密,GAP-43、Syn表达增强,NGF、BDNF、NT-3含量升高,其中复方血栓通胶囊低剂量组效果显著(P<0.05)。结论 复方血栓通胶囊可能通过促进GAP-43、Syn表达并提高神经营养因子含量、从而诱导轴突再生,提高神经可塑性,发挥神经保护作用。

关键词: 复方血栓通胶囊, 神经可塑, 脑缺血再灌注, 神经营养因子, 小鼠

Abstract: To observe the influence of Fufang Xueshuantong(Compound for Resolving Thrombosis) Capsule (FFXST Capsule) on neuroplasticity in mice with cerebral ischemia-reperfusion (CIR) and discuss the relevant mechanism. Methods Male CIR mice were randomly divided into sham-operation group, CIR group, low-dose (0.75 g/kg), mid-dose (1.5 g/kg) and high-dose (2.25 g/kg) FFXST Capsule groups, and Buchang Naoxintong Capsule (BCNXT Capsule) group (0.55 g/kg). Each group was divided randomly into 1-d group 7-d group and 14-d group (each n=10). The model was established by using middle cerebral artery occlusion (MCAO). The sham-operation group was only given anesthesia and blood vessel separation without ligation and embolization. Other groups were orally given medicinals once a day. The status of neurological dysfunction was reviewed through neurological scoring, adhesive tape removal and forelimb strength determination experiment. The healthy condition of mice was observed through monitoring mortality. The morphologic changes and expressions of GAP-43, Syn, in cortical neurons of ischemic zone were detected by using Nissl staining and immunohistochemical staining (IHC). The content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophic factor-3 (NT-3) was detected by using ELISA, and levels of neurotrophic factors were observed after CIR injury. Results Compared with sham-operation group, the significant neurological impairment and motor disorders were observed in CIR group(P<0.05) with higher mortality, shallow Nissl’ staining vacuoles and sparse arrangement in the tissue around ischemic zone. The expressions of GAP-43 and Syn decrease and content of NGF, BDNF and NT-3 increased in CIR group. Compared with CIR group, the neurological dysfunction had been relieved and mortality was reduced in FFXST Capsule groups in different doses, with deepened Nissl staining, less vacuoles and more tight arrangement. The expressions of GAP-43 and Syn increased and content of NGF, BDNF and NT-3 increased in FFXST Capsule groups. The above effect were more significantly in low-dose FFXST Capsule group(P<0.05). Conclusion FFXST Capsule can induce axonal regenera tion, improve neuroplasticity and play the role of neuroprotection may through promoting GAP 43 and Syn expressions, and increasing neurotrophic factor content.

Key words: Fufang Xueshuantong(Compound for Resolving Thrombosis) Capsule, neuro plasticity, cerebral ischemia-reperfusion, neurotrophic factor, mice

中图分类号: 

  • R285.5