中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 2030-2040.doi: 10.4103/1673-5374.308102

• 原著:退行性病与再生 • 上一篇    下一篇

熊果苷能有效改善帕金森病表现：基于腺苷受体和环状单磷酸腺苷的作用

  

  • 出版日期:2021-10-15 发布日期:2021-03-19

Arbutin effectively ameliorates the symptoms of Parkinson’s disease: the role of adenosine receptors and cyclic adenosine monophosphate

Jie Zhao1, Manish Kumar2, Jeevan Sharma2, Zhihai Yuan3, *   

  1. 1Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China; 2Department of Pharmacology, Swift School of Pharmacy, Rajpura (Patiala), Punjab, India; 3Department of Neurosurgery, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi Province, China
  • Online:2021-10-15 Published:2021-03-19
  • Contact: Zhihai Yuan, MS, yzhysd@sina.com.

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摘要：

基底神经节腺苷能信号和多巴胺能信号的拮抗性交流表明，抑制腺苷A2A受体-环磷酸腺苷通路可恢复多巴胺的传递，从而减轻帕金森病的运动症状。熊果苷是一种天然糖苷，具有抗氧化、抗炎和神经保护作用，是否有可能减轻帕金森病症状？此次实验旨在验证其作用及机制。实验给予瑞士白化病小鼠连续4d腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导建立帕金森病模型，同时腹腔注射熊果苷（50和100 mg/kg）7d。结果显示， 熊果苷可明显减轻帕金森病模型小鼠大脑黑质和纹状体中脂质过氧化、亚硝化应激和炎症水平，降低内源性抗氧化剂的活性，减少多巴胺、3,4-二羟基苯基乙酸、高香草酸和γ-氨基丁酸水平，减轻纹状体中的神经变性，同时减少旷场测试、僵直测试、爬杆测试和转杆测试的异常运动表现，且其效果与美多巴（madopar）接近。而腹腔注射A2AR激动剂CGS21680（0.5 mg/kg）可减弱熊果苷的作用，而注射腺苷酸环化酶激动剂forskolin（3 mg/kg）则能增强熊果苷介导的改善。表明熊果苷通过抑制腺苷A2A受体功能以及增强环磷酸腺苷的作用可改善帕金森病的表现。实验于2019-11-17经动物伦理委员会（1616/PO/Re/S/12/CPCSEA）批准，批准号IAEC/2019/010。

https://orcid.org/0000-0002-1589-1542 (Jie Zhao); https://orcid.org/0000-0001-6697-544X (Manish Kumar); 
https://orcid.org/0000-0001-7087-7615 (Jeevan Sharma); https://orcid.org/0000-0002-0157-2719 (Zhihai Yuan)

关键词:

熊果苷, 帕金森病, 多巴胺, GABA, 炎症, 氧化应激, 黑质, 纹状体, forskolin, CGS21680

Abstract: An antagonistic communication exists between adenosinergic and dopaminergic signaling in the basal ganglia, which suggests that the suppression of adenosine A2A receptors-cyclic adenosine monophosphate pathway may be able to restore the disrupted dopamine transmission that results in motor symptoms in Parkinson’s disease (PD). Arbutin is a natural glycoside that possesses antioxidant, anti-inflammatory, and neuroprotective properties. The purpose of this study was to investigate whether arbutin could ameliorate the symptoms of PD and to examine the underlying mechanism. In this study, Swiss albino mouse models of PD were established by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 4 successive days, with the concurrent intraperitoneal administration of arbutin (50 and 100 mg/kg) for 7 days. The results showed that arbutin significantly reduced lipid peroxidation, total nitrite levels, and inflammation in the substantia nigra and striatum of PD mouse models. In addition, arbutin decreased the activity of endogenous antioxidants, reduced the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and γ-aminobutyric acid, and minimized neurodegeneration in the striatum. Arbutin also reduced the abnormal performance of PD mouse models in the open field test, bar test, pole test, and rotarod test. The therapeutic efficacy of arbutin was similar to that of madopar. The intraperitoneal injection of the A2AR agonist CGS21680 (0.5 mg/kg) 
attenuated the therapeutic effects of arbutin, whereas the intraperitoneal injection of forskolin (3 mg/kg) enhanced arbutin-mediated improvements. These findings suggest that arbutin can improve the performance of PD mouse models by inhibiting the function of the A2AR and enhancing the effects of cyclic adenosine monophosphate. This study was approved by the Institutional Animal Ethics Committee (1616/PO/Re/S/12/CPCSEA) on November 17, 2019 (approval No. IAEC/2019/010).

Key words: arbutin, CGS21680, dopamine, forskolin, GABA, inflammation, oxidative stress, Parkinson’s disease, striatum, substantia nigra

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