摘要
目的探讨复方地黄方对腺病毒(AAV)介导的α-syn基因过表达帕金森病(PD)模型大鼠α-突触核蛋白(α-syn)异常聚集及错误折叠的机制,以探索PD的发病机制及复方地黄方在治疗PD中的“增效减毒”机制。方法通过构建AAV介导的α-syn基因过表达PD大鼠模型,在治疗4周后取出各组大鼠纹状体、黑质,应用Tunel染色和Western Blot检测神经元凋亡和相关蛋白表达水平情况。结果Tunel染色发现,复方地黄方干预4周后大鼠黑质和纹状体神经元凋亡情况有所缓解(P<0.05或P<0.01)。Western Blot研究发现,复方地黄方干预后大鼠脑中α-syn、GSK3β、P-GSK3β(Tyr216)蛋白表达水平均有下降(P<0.05或P<0.01),而P-GSK3β(Ser9)、β-Catenin蛋白表达水平显著上升(P<0.01)。结论复方地黄方可能是一种潜在的PD神经保护剂,可能通过调控GSK3β/β-Catenin信号通路,缓解大鼠黑质和纹状体神经元细胞凋亡,起到神经保护作用。
Objective To investigate the mechanism of Compound Dihuang Formula(复方地黄方)on the abnormal aggregation and misfolding ofα-synuclein(α-syn)in a rat model of Parkinson's disease(PD)induced by adenovirus(AAV)mediated overexpression ofα-syn gene,so as to explore the pathogenesis of PD and the“synergistic and attenuated”mechanism of Compound Dihuang Formula in the treatment of PD.Methods AAV-mediatedα-syn gene overexpression was established in PD rats.After 4 weeks of treatment,the striatum and substantia nigra of rats in each group were extracted,and neuronal apoptosis and related protein expression levels were detected by Tunel staining and Western Blot.Results Tunel staining showed that the neuronal apoptosis of substantia nigra and striatum of rats was alleviated after 4 weeks intervention by Compound Dihuang Formula(P<0.05 or P<0.01).WB study showed that the protein expression levels ofα-syn,GSK3βand p-GSK3β(Tyr216)in the brain of rats with prognosis of Compound Dihuang Formula were decreased(P<0.05 or P<0.01),while the protein expression levels of p-GSK3β(Ser9)andβ-catenin were significantly increased(P<0.01).Conclusion Compound Dihuang Formula may be a potential neuro protective agent for PD,which may relieve the apoptosis of neurons in the substantia nigra and striatum of rats by regulating the GSK3β/β-catenin signaling pathway and play a neuroprotective role.
作者
滕龙
洪芳
何建成
TENG Long;HONG Fang;HE Jiancheng(Zhejiang Hospital,Hangzhou 310013,Zhejiang,China;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《辽宁中医杂志》
CAS
2022年第4期202-204,225-226,共5页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81573899)
浙江省自然基金(LY18H270015)
浙江省中医药优秀青年人才基金(2016ZQ005)
关键词
帕金森病
α-syn
复方地黄方
机制
Parkinson's disease
α-syn
Compound Dihuang Formula(复方地黄方)
mechanism
作者简介
滕龙(1985-),男,甘肃武威人,主治医师,硕士研究生,研究方向:中医药防治心脑血管疾病的基础和临床研究;通讯作者:何建成(1966-),男,甘肃天水人,教授,博士研究生导师,博士,研究方向:中医四诊、证候及心脑血管疾病的基础与临床研究,E-mail:hjc8163@163.com。
