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 (2): 326-331.doi: 10.4103/1673-5374.177742

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

一种新型糖尿病药物的神经保护作用

  

  • 收稿日期:2015-12-17 出版日期:2016-02-15 发布日期:2016-02-15

Neuroprotective role of (Val8)GLP-1-Glu-PAL in an in vitro model of Parkinson’s disease

Lin Li 1, Ke Liu 1, Juan Zhao 1, Christian Holscher 2, 3, Guang-lai Li 2, Yue-ze Liu 2   

  1. 1 Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi Province, China
    2 Second Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, China
    3 Biomedical and Life Sciences, Lancaster University, Lancaster, UK
  • Received:2015-12-17 Online:2016-02-15 Published:2016-02-15
  • Contact: Christian Holscher or Yue-ze Liu, Ph.D., yuezeliu@163.com.
  • Supported by:

    This study was supported by a grant from the Shanxi Science and Technology Department of China, No. 2011081060; a grant from Shanxi Scholarship Council of China, No. 2011-44; and a grant from the Cure Parkinson’s Trust UK to CH.

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摘要：

胰高血糖素样多肽1对多种神经退行性疾病动物模型具有神经保护作用，其类似物(Val8)GLP-1-Glu-PAL是否也具有神经保护作用呢？我们以鱼藤酮诱导建立小鼠大脑神经元帕金森病模型，在造模前以(Val8)GLP-1-Glu-PAL预处理2h。结果显示，鱼藤酮剂量依赖性减少神经元的活性，而经(Val8)GLP-1-Glu-PAL预处理可剂量依赖性抑制这种变化，并能减缓鱼藤酮造成的神经元中procaspase-3和Bcl-2水平下降及cleaved caspase-3水平上升，且单纯(Val8)GLP-1-Glu-PAL处理不影响神经元的活性。表明胰高血糖素样多肽1类似物(Val8)GLP-1-Glu-PAL有成为对帕金森病治疗的神经保护作用药物的潜力。

关键词: 神经再生, 帕金森病, 胰高血糖素样多肽1, 神经退行性疾病, 细胞凋亡, Bcl-2, 神经元, 鱼藤酮

Abstract:

The growth factor glucagon-like peptide-1 (GLP-1) is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue, (Val8)GLP-1-Glu-PAL, which has advantages over older analogues, such as improvement of hippocampal neurogenesis, glucose homeostasis, and insulin secretion. We established an in vitro model of Parkinson’s disease using the mitochondrial stressor rotenone in primary cultured mouse neurons pretreated with (Val8)GLP-1-Glu-PAL. (Val8)GLP-1-Glu-PAL alone did not affect neuronal viability, but prevented the rotenone-induced reduction in cell viability in a dose-dependent manner. In addition, (Val8)GLP-1-Glu-PAL pretreatment prevented rotenone-induced proapoptotic changes manifesting as downregulation of procaspase-3 and Bcl-2 and upregulation of cleaved caspase-3. These results demonstrate that the novel agent (Val8)GLP-1-Glu-PAL shows promise as a drug treatment for Parkinson’s disease.

Key words: nerve regeneration, Parkinson’s disease,  , GLP-1, neurodegenerative disease, apoptosis, caspase-3, Bcl-2, cellular culture, rotenone, neural regeneration