摘要
目的:探究紫红獐牙菜(口山)酮提取物对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)致帕金森病(Parkinson’s disease,PD)小鼠的神经保护作用及其作用机制。方法:小鼠灌胃(ig)给药14 d(9.0 mg·kg-1),后5 d腹腔注射(ip,30 mg·kg^-1)MPTP建立模型,之后进行酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组织化学染色、非标记定量蛋白质组学法检测和生物信息学分析。结果:紫红獐牙菜(口山)酮提取物可减少MPTP致帕金森小鼠脑黑质部位多巴胺能神经元的丢失;筛选出150个给药组与模型组之间的差异表达蛋白质;其潜在作用信号通路为泛素介导的蛋白水解、核糖体、硫胺素代谢通路,核心差异蛋白有Hspa13,Rplp1,Rplp2和Rps8。结论:紫红獐牙菜(口山)酮提取物对MPTP所致帕金森小鼠具有神经保护作用,其潜在机制可能包括减少α-syn错误折叠,抑制星形胶质细胞过度活化,减少活性氧簇,减轻炎症反应等。
Objective:To study the neuroprotective effect and mechanism of xanthone extract from Swertia punicea Hemsl on the MPTP-induced Parkinson’s disease in mouse.Methods:The mice were intragastrically administered a dose of 9.0 mg·kg^-1 for 14 consecutive days.The PD model was induced by giving MPTP(30 mg·kg-1,ip)in the last 5 days since the 10 th day of dosing.Then TH immunohistochemical staining,label-free quantitative proteomics,and bioinformatics analysis were performed.Results:Xanthone extract from Swertia punicea Hemsl reduced the loss of dopaminergic neurons in the substantia nigra of the MPTP-induced Parkinsonian mouse.A total of 150 proteins which expressed differentially between the drug-administration group and the model group were found.The main signal pathways for these enriched differential proteins were ubiquitin mediated proteolysis,ribosome,and thiamine metabolism pathway.The core differential proteins were Hspa13,Rplp1,Rplp2,and Rps8.Conclusion:The xanthone extract from Swertia punicea Hemsl has neuroprotective effect on MPTP-induced Parkinson’s disease in mouse.Potential mechanism of the extract on the anti-MPTP-induced PD effect may includereducingα-syn misfolding,astrocyte overactivation,reactive oxygen species,and inflammation.
作者
高泽宇
郭涌斐
孙懿
林铭
蒲小平
赵欣
GAO Ze-yu;GUO Yong-fei;SUN Yi;LIN Ming;PU Xiao-ping;ZHAO Xin(Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第1期48-54,共7页
Chinese Journal of New Drugs
基金
国家自然科学基金(U1603128)
北京大学医学科技创新平台发展基金-医学交叉种子基金资助项目(BMU2017MX004)
国家“重大新药创制”科技重大专项资助项目(2018ZX09711001-009-006).
