中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (7): 1195-1203.doi: 10.4103/1673-5374.235031

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

中药复方侯氏黑散及其组分可促进缺血性脑损伤神经轴突的再生

  

  • 收稿日期:2018-05-23 出版日期:2018-07-15 发布日期:2018-07-15
  • 基金资助:

    中国国家自然科学基金项目（81373526）

Houshiheisan and its components promote axon regeneration after ischemic brain injury

Yue Lu1, 2, Flora Hsiang1, 2 Jia-Hui Chang1, 2, Xiao-Quan Yao1, 2, Hui Zhao1, 2, Hai-Yan Zou1, 2, Lei Wang1, 2, Qiu-Xia Zhang1, 2   

  1. 1 School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
    2 Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing, China
  • Received:2018-05-23 Online:2018-07-15 Published:2018-07-15
  • Contact: Qiu-Xia Zhang, M.D.,zqx26@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81373526.

PDF

254

摘要：

中药复方侯氏黑散是一种经典的中国中药组方，含有黄芩、防风、桂枝、川芎、白芷、桔梗、白术、茯苓、干姜、当归、人参、黄芩和牡蛎，其中黄芩、防风、桂枝、川芎、白芷和桔梗有散寒功能，白术、茯苓、干姜、当归和人参有补益功能，有大量的随机对照临床试验证明其治疗卒中有效，但其机制尚未明确。由于神经轴突重塑被认为是神经保护和再生的重要机制，因此实验设计了观察侯氏黑散对脑缺血后神经轴突的修复作用及机制。实验以结扎右侧大脑中动脉建立局灶脑缺血大鼠模型，在造模后6h首次灌胃10.5 g/kg侯氏黑散或7.7 g/kg散寒药或2.59 g/kg 补益药，而后每24h这样给药一次。连续灌胃7d。结果显示，侯氏黑散及其组分散寒药和补益药均能有效降低脑缺血大鼠的神经功能缺损评分，减轻神经轴突和神经元病变，并能够减少海马组织中对神经轴突重塑有抑制作用的淀粉样前体蛋白、神经突生长抑制蛋白A、Rho家族小GTP酶A和Rho相关激酶2的表达，并且增加促进神经轴突重塑的蛋白生长相关蛋白43、微管相关蛋白2、netrin-1、Rac1和细胞分裂周期42的表达，且侯氏黑散的作用比单独的散寒药或补益药的干预更为有效。表明侯氏黑散及其组分散寒药和补益药可通过调节Nogo-A/RhoA/Rock2和Netrin-1/DCC/Cdc42信号通路，均促进神经轴突的修复，从而促进脑缺血后神经再生，且侯氏黑散效果最为明显。

orcid:0000-0001-6751-5699(Qiu-Xia Zhang)

关键词: 侯氏黑散, 散寒药, 补益药, 脑缺血, 轴索修复, Nogo-A/RhoA/Rock2信号通路, Netrin-1/Rac1/Cdc42信号通路, 神经保护, 神经再生

Abstract:

Houshiheisan, a classic prescription in traditional Chinese medicine, contains Flos Chrysanthemi, Radix Saposhnikoviae, Ramulus Cinnamomi,Rhizoma Chuanxiong, Radix et Rhizoma Asari, Radix Platycodonis, Rhizoma Atractylodis macrocephalae, Poria, Rhizoma Zingiberis, Radix Angelicae sinensis, Radix et Rhizoma Ginseng, Radix Scutellariae and Concha Ostreae. According to traditional Chinese medicine theory, Flos Chrysanthemi, Radix Saposhnikoviae, Ramulus Cinnamomi, Rhizoma Chuanxiong, Radix et Rhizoma Asari and Radix Platycodonis are wind-dispelling drugs; Rhizoma Atractylodis macrocephalae, Poria, Rhizoma Zingiberis, Radix Angelicae sinensis and Radix et Rhizoma Ginseng are deficiency-nourishing drugs. A large number of randomized controlled trials have shown that Houshiheisan is effective in treating stroke, but its mechanism of action is unknown. Axonal remodeling is an important mechanism in neural protection and regeneration. Therefore, this study explored the effect and mechanism of action of Houshiheisan on the repair of axons after cerebral ischemia. Rat models of focal cerebral ischemia were established by ligating the right middle cerebral artery. At 6 hours after model establishment, rats were intragastrically administered 10.5 g/kg Houshiheisan or 7.7 g/kg wind-dispelling drug or 2.59 g/kg deficiency-nourishing drug. These medicines were intragastrically administered as above every 24 hours for 7 consecutive days. Houshiheisan,and its wind-dispelling and deficiency-nourishing components reduced the neurological deficit score and ameliorated axon and neuron lesions after cerebral ischemia. Furthermore, Houshiheisan, and its wind-dispelling and deficiency-nourishing components decreased the expression of proteins that inhibit axonal remodeling: amyloid precursor protein, neurite outgrowth inhibitor protein A (Nogo-A), Rho family small GTPase A (RhoA) and Rho-associated kinase 2 (Rock2), and increased the expression of growth associated protein-43, microtubule-associated protein-2, netrin-1, Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42). The effect of Houshiheisan was stronger than wind-dispelling drugs or deficiency-nourishing drugs alone. In conclusion, Houshiheisan, and wind-dispelling and deficiency-nourishing drugs promote the repair of axons and nerve regeneration after cerebral ischemia through Nogo-A/RhoA/Rock2 and Netrin-1/Rac1/Cdc42 signaling pathways. These effects are strongest with Houshiheisan.

Key words: nerve regeneration, Houshiheisan, wind-dispelling drug, deficiency-nourishing drug, cerebral ischemia, Nogo-A/RhoA/Rock2 signaling pathway, axonal recovery, Netrin-1/Rac1/Cdc42 signaling pathway, neuroprotection, neural regeneration