中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (10): 1625-1632.doi: 10.4103/1673-5374.193242

• 原著:退行性病与再生 • 上一篇    下一篇

熟地平颤颗粒抑制帕金森大鼠大脑黑质神经细胞凋亡的神经保护作用

  

  • 收稿日期:2016-08-21 出版日期:2016-10-31 发布日期:2016-10-31
  • 基金资助:
    中国国家自然科学基金项目（81302926, 30472207）；上海市科委重大项目（15401970100）；上海市卫计委项目（ZY3-RCPY-2-2005）

Anti-apoptotic e?ect of Shudipingchan granule in the substantia nigra of rat models of Parkinson’s disease

Qing Ye1, Xiao-lei Yuan1, Jing He1, Jie Zhou1, Can-xing Yuan1, *, Xu-ming Yang2, *   

  1. 1 Department of Neurology, Longhua Hospital Afliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China 2 College of Acupuncture and Manipulation, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Received:2016-08-21 Online:2016-10-31 Published:2016-10-31
  • Contact: Can-xing Yuan or Xu-ming Yang, ycanxing@hotmail.com or fslbest@126.com.
  • Supported by:
    This study was fnancially supported by the National Natural Science Foundation of China, No. 81302926, 30472207; the Major Project of Shanghai Science and Technology Commission of China, No. 15401970100; the Shanghai Municipal Commission of Health and Family Planning of China, No. ZY3-RCPY-2-2005.

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摘要：

左旋多巴是治疗帕金森病的金标准药物，可有效缓解患者的临床症状，但不能延迟多巴胺能神经元凋亡的进程，且长期使用会造成运动并发症。实验以6-羟多巴胺注射大鼠黑质致密部和中脑腹侧被盖区建立帕金森病模型，然后腹腔注射20mg/kg左旋多巴和/或灌胃由熟地黄、山茱萸、桑寄生、天麻、僵蚕、葛根、莪术、丹参、天南星和全蝎制成的熟地平颤颗粒(7.5mL/kg, twice a day)，治疗4周。见长期使用左旋多巴的帕金森病模型大鼠通过激活大脑黑质中ERK通路和下游凋亡因子，加速黑质细胞凋亡，造成行为学症状恶化；联合熟地平颤颗粒治疗后，大鼠黑质中磷酸化ERK1/2和促凋亡蛋白Bax表达减少，酪氨酸羟化酶和抗凋亡蛋白Bcl-2表达增加，大脑黑质细胞凋亡明显减少，运动障碍也明显改善。提示熟地平颤颗粒可通过抑制ERK的磷酸化和下调抗凋亡基因的表达，抑制黑质神经细胞凋亡，与左旋多巴合用，可以更好的缓解帕金森病的症状。 

orcid: 0000-0001-6220-7590 (Can-xing Yuan), 0000-0002-2880-2609 (Xu-ming Yang) ,

关键词: 神经再生, 帕金森病, 左旋多巴, 大脑黑质, 细胞凋亡, 熟地平颤颗粒, ERK通路, 行为

Abstract: Levodopa is the gold-standard treatment for Parkinson’s disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the e?ect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson’s disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily) with or without Shudipingchan granule (7.5 mL/kg intragastrically, twice daily), for 4 weeks. Te long-term use of levodopa accelerated apoptosis of nigral cells and worsened behavioral symptoms by activating the extracellular signal-regulated kinase pathway and downstream apoptotic factors. However, administration of Shudipingchan granule with levodopa reduced expression of phosphorylated extracellular signal-regulated kinase 1/2 and Bax, increased tyrosine hydroxylase and Bcl-2, reduced apoptosis in the substantia nigra, and markedly improved dyskinesia. Tese fndings suggest that Shudipingchan granule suppresses neuronal apoptosis by inhibiting the hyperphosphorylation of extracellular signal-regulated kinase and downregulating expression of anti-apoptotic genes. Shudipingchan granule, used in combination with levodopa, can e?ectively reduce the symptoms of Parkinson’s disease.

Key words: nerve regeneration, Parkinson’s disease, levodopa, substantia nigra, apoptosis, Shudipingchan granule, extracellular signal-regulated kinase pathway, behavior, neural regeneration