摘要
目的探讨帕金森病动物模型和细胞模型中α-突触核蛋白与Wnt/β-catenin信号通路的相关关系及其导致神经元损伤的可能机制。方法在动物水平和细胞水平上应用western blotting方法、流式细胞术、免疫荧光法等方法研究α-synuclein与Wnt/β-catenin信号通路关键信号分子GSK-3β的表达关系及其对细胞活性的影响。结果α-syn转基因小鼠脑组织中α-synuclein、p-GSK-3β蛋白表达量均明显增加,与对照组和MPTP组相比具有统计学差异(P <0. 05);α-syn过表达组SH-SY5Y细胞中α-synuclein、p-GSK-3β表达量较对照组及MPP+损伤组明显升高,结果具有统计学差异(P <0. 05);阿立哌唑预处理组α-synuclein较对照组及MPP+组明显增加,p-GSK-3β与对照组及MPP+组差异不具有统计学差异;阿立哌唑预处理组细胞活性明显高于α-syn过表达组,细胞凋亡率较α-syn过表达组明显下降,差异具有统计学意义(P <0. 05);免疫荧光法示α-synuclein与p-GSK-3β存在共定位关系。结论α-synuclein可能通过抑制Wnt/β-catenin信号通路导致神经元损伤,从而参与帕金森病的发病机制。
Objective To investigate the effect ofα-synuclein(α-syn)on Wnt/β-catenin signaling pathway in Parkinson’s disease animal models and cell models and the possible mechanism of neuronal injury.Methods Western blotting,flow cytometry,immunofluorescence and other methods were used to detect the expression ofα-synuclein and the key signal molecule GSK-3βin Wnt/β-catenin signaling pathway and its effect on cell viability at the animal and cell levels.Results The expressions ofα-synuclein and p-GSK-3βin the brain tissue ofα-syn transgenic mice increased significantly,compared with the control group and MPTP group(P<0.05).The expression levels ofα-synuclein and p-GSK-3βin SH-SY5Y cells ofα-syn overexpression group were significantly higher than those in the control group and MPP+injury group,and the results were statistically significant(P<0.05).Theα-synuclein in the aripiprazole pretreatment group was significantly increased compared with the control group and the MPP+group.There was no significant difference in p-GSK-3βbetween the control group and the MPP+group.The cell viability of aripiprazole pretreatment group was significantly higher than that ofα-syn overexpression group,and the apoptosis rate was significantly lower than that ofα-syn overexpression group,the difference was statistically significant(P<0.05).Immunofluorescence showed a colocalization relationship betweenα-synuclein and p-GSK-3β.Conclusionα-synuclein may participate in the pathogenesis of Parkinson’s disease by inhibiting the Wnt/β-catenin signaling pathway leading to neuronal damage.
作者
程丽萍
王浩
车峰远
亓法英
CHENG Liping;WANG Hao;CHE Fengyuan(Qingdao University,Eleventh Clinical Medical College-Linyi People’s Hospital,Qingdao 266000,China)
出处
《中风与神经疾病杂志》
CAS
2019年第1期10-14,共5页
Journal of Apoplexy and Nervous Diseases
基金
山东省自然科学基金(No.ZR2014HL041)
作者简介
通讯作者:车峰远,E-mail:che1971@126.com.
