天麻对帕金森小鼠神经元保护作用机制的转录组学分析

张大燕; 文欢; 王伟; 赵灵; 彭成; 高继海

doi:10.13422/j.cnki.syfjx.20181303

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天麻对帕金森小鼠神经元保护作用机制的转录组学分析

组学与生物信息学 | 更新时间：2024-01-04

- 天麻对帕金森小鼠神经元保护作用机制的转录组学分析
- Transcriptome Analysis of Protective Mechanism of Gastrodiae Rhizoma on Neurons of Parkinson Mice
- 中国实验方剂学杂志 2018年24卷第16期页码：73-81
- 作者机构：
- 作者简介：
- 基金信息：
  
  四川省科技支撑计划项目（2014FZ0121，2015FY111500-140）;中药资源四川省青年科技创新研究团队项目（2015TD0028）
- DOI：10.13422/j.cnki.syfjx.20181303
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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张大燕, 文欢, 王伟, 等. 天麻对帕金森小鼠神经元保护作用机制的转录组学分析[J]. 中国实验方剂学杂志, 2018,24(16):73-81.

ZHANG Da-yan, WEN Huan, Wang Wei, et al. Transcriptome Analysis of Protective Mechanism of Gastrodiae Rhizoma on Neurons of Parkinson Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(16): 73-81.
张大燕, 文欢, 王伟, 等. 天麻对帕金森小鼠神经元保护作用机制的转录组学分析[J]. 中国实验方剂学杂志, 2018,24(16):73-81. DOI： 10.13422/j.cnki.syfjx.20181303.

ZHANG Da-yan, WEN Huan, Wang Wei, et al. Transcriptome Analysis of Protective Mechanism of Gastrodiae Rhizoma on Neurons of Parkinson Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(16): 73-81. DOI： 10.13422/j.cnki.syfjx.20181303.

摘要

目的：研究天麻水煎液对A53T α-突触核蛋白（α-synuclein）转基因帕金森小鼠的治疗作用，及其对凋亡相关通路表达的影响。方法：以A53T α-synuclein转基因帕金森小鼠为实验对象，设置模型组、天麻组、空白组、阳性组（美多芭组）；采用基因型鉴定法、苏木素-伊红（HE）染色法和行为学实验测定小鼠中脑黑质神经元病理改变，以判断造模是否成功；Illumina HiSeq 2500平台测序，检测天麻组所有基因转录本的差异表达，通过功能注释和富集分析筛选出与帕金森保护相关的基因及代谢途径。结果：预给予天麻水煎液治疗后能改善A53T α-synuclein转基因帕金森小鼠中脑黑质神经元病变，转录数据分析显示其作用机制主要涉及原癌基因大鼠肉瘤（Ras），p38丝裂原活化蛋白激酶（p38 MAPK）及Ca2+等相关凋亡途径的抑制或激活调控。与模型组相比，天麻组中多巴胺第三受体，神经肽Y，Ras蛋白特异鸟嘌呤核苷酸释放因子1，钙/钙调蛋白依赖的磷酸二酯酶1A等基因表达上调，原癌基因c-Fos，p38 MAPK和人促分裂素原活化蛋白激酶激活的蛋白激酶3等凋亡基因表达下调。结论：天麻水煎液对A53T α-synuclein转基因帕金森小鼠具有一定的治疗作用，其机制可能与抑制多种凋亡相关信号通路有关。

Abstract

Objective: To study on the therapeutic effect of Gastrodiae Rhizoma decoction on A53T α-synuclein transgenic Parkinson mice and its influence on the expression of apoptosis related pathways. Method: A53T α-synuclein transgenic mice with Parkinson disease were used as experimental subjects

and model group

Gastrodiae Rhizoma group

blank group and positive group(madopar group) were also set up.The pathological changes of substantia nigra neurons in mice were determined by genotype identification

hematoxylin-eosin(HE) staining and behavioural experiment to judge the success of the model establishment

the Illumina HiSeq 2500 platform sequencing technologies was used to detect differential expression of transcripts of all genes in Gastrodiae Rhizoma group.The genes related to Parkinson's protection and metabolic pathways were screened by functional annotation and enrichment analysis. Result: It could improve the substantia nigra neuron pathological changes in A53T α-synuclein transgenic Parkinson mice after treating Gastrodiae Rhizoma decoction

and transcriptome analysis showed that the mechanism mainly involved the inhibition or activation of proto oncogene of rat sarcoma(Ras)

p38 mitogen activated protein kinase(p38 MAPK) and Ca2+ related apoptosis pathways.Compared with the model group

the expression of dopamine third receptor(DRD3)

neuropeptide Y(NPY)

Ras protein specific guanine nucleotide releasing factor 1 (RASGRP1)

calcium/calmodulin-dependent 3'

5'-phosphodiesterase 1A(PDE1A) in Gastrodiae Rhizoma group were up-regulated

and apoptotic genes

such as proto oncogene of c-Fos

p38 MAPK and protein kinase 3 activated by human mitogen activated protein kinase (MAPKAPK3) were down-regulated. Conclusion: Gastrodiae Rhizoma decoction has a certain therapeutic effect on A53T α-synuclein transgenic Parkinson mice

its mechanism may be mainly related to the inhibition of many apoptotic related signaling pathways.

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