中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (2): 361-368.doi: 10.4103/1673-5374.265557

• 原著:退行性病与再生 • 上一篇    

绞股蓝乙醇提取物抑制表达突变体A53T人α-突触核蛋白的转基因小鼠中脑多巴胺能神经元细胞死亡

  

  • 出版日期:2020-02-15 发布日期:2020-05-25
  • 基金资助:

    韩国国家研究基金会基金(2016R1D1A3B03930722）

Ethanol extract from Gynostemma pentaphyllum ameliorates dopaminergic neuronal cell death in transgenic mice expressing mutant A53T human alpha-synuclein

Hyun Jin Park1, 2, Ting Ting Zhao1, Seung Hwan Kim3, Chong Kil Lee1, 2, Bang Yeon Hwang1, Kyung Eun Lee1, Myung Koo Lee1, 2   

  1. 1 Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
    2 Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
    3 Department of Social Physical Education, Songwon University, Gwangju, Republic of Korea
  • Online:2020-02-15 Published:2020-05-25
  • Contact: Myung Koo Lee, PhD,myklee@chungbuk.ac.kr.
  • Supported by:
    This study was supported by the National Research Foundation of Korea, grant No. 2016R1D1A3B03930722 (to MKL), Republic of Korea.

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摘要：

绞股蓝（Gynostemma pentaphyllum）含有各种生物活性绞股蓝总皂苷。绞股蓝乙醇提取物对1-甲基-4-苯基-1,2,3,6-四氢吡啶和6-羟基多巴胺诱导的多巴胺能神经元的死亡具有抑制作用。为了解绞股蓝乙醇提取物（包括绞股蓝总皂苷）对A53Tα-突触核蛋白转基因帕金森病小鼠模型中脑多巴胺能神经元细胞死亡的抑制作用，实验按50mg/kg/d剂量将绞股蓝乙醇提取物和绞股蓝皂苷灌胃干预A53T小鼠20周。与野生型小鼠比较，A53T小鼠中脑a-突触核蛋白免疫阳性细胞和a-突触核蛋白磷酸化表达增加，绞股蓝乙醇提取物干预可抑制这种变化。用绞股蓝乙醇提取物处理还可调节a-突触核蛋白过表达引起的酪氨酸羟化酶，细胞外信号调节激酶（ERK1 / 2），Bcl-2相关死亡启动子(Ser112位点) （BadSer112）和c-Jun N末端激酶（JNK1 / 2）的磷酸化表达降低。同时, 绞股蓝乙醇提取物延长了A53T小鼠穿梭被动回避实验潜伏期，缩短了高架十字迷宫系统转移潜伏期。绞股蓝总皂苷治疗显示出与绞股蓝乙醇提取物类似的效果。总之，包括绞股蓝乙醇提取物通过调节ERK1/2-BadSer112-JNK1/2信号抑制帕金森病小鼠α-突触核蛋白过表达致中脑多巴胺能神经细胞死亡。该研究于2016年9月21日经忠北国立大学动物伦理委员会（批准号CBNUA-956-16-01）批准。

orcid: 0000-0002-3327-3481 (Myung Koo Lee)

关键词:

绞股蓝乙醇提取物, A53T, α-突触核蛋白转基因小鼠, 帕金森病, ERK1/2, JNK1/2, 学习记忆功能

Abstract: Gynostemma (G.) pentaphyllum (Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum (GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53T α-synuclein transgenic mouse models of PD (A53T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53T mice for 20 weeks. α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase (ERK1/2), Bcl-2-associated death promoter (Bad) at Ser112, and c-Jun N-terminal kinase (JNK1/2) due to α-synuclein overexpression. In the A53T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University (approval No. CBNUA-956-16-01) on September 21, 2016.

Key words: A53T α-synuclein genetic mice, ERK1/2, gynostemma pentaphyllum, gypenosides, Parkinson’s disease, retention transfer latency time