中国药理学通报2018，Vol.34Issue(6)：797-803,7.DOI:10.3969/j.issn.1001-1978.2018.06.012
虫草素对MPTP诱导的小鼠多巴胺能神经元损伤的保护作用及其机制
The protective effects of cordycepin on MPTP-induced dopaminergic neuron damage in mice and its mechanism
摘要
Abstract
Aim To observe the protective effects of cordycepin ( Cor) on dopaminergic neurons in 1-meth-yl-4-phenyl-1 , 2 , 3 , 6-tetrahydropyridine ( MPTP )-in-duced mouse model of Parkinson's disease ( PD) and to explore its mechanism. Methods C57BL/6 mice were administered with MPTP to establish the PD mod-el. Mice in Cor groups were pretreated with Cor (2.5,5.0 and 10.0 mg·kg-1 ) by intragastric administra-tion, respectively. The motor functions of the mice were observed in the open-field test, rotarod test and pole test. The content of DA, the numbers of TH-im-munoreactive cells and apoptotic cells were measured respectively by HPLC-ECD, immunohistochemistry staining and TUNEL staining. The expression of apop-tosis related proteins and MAPK signaling pathway-re-lated proteins ( p38 , p-p38 , ERK1/2 , p-ERK1/2 JNK1/2 and p-JNK1/2 ) were determined by Western blot. Results Cor could significantly improve the mo-tor dysfunction in PD mice. The contents of DA, DOPAC and HVA in the striatum remarkably increased after administration of Cor in MPTP-induced mice. Mo-reover, Cor could obviously reduce both the loss of TH-immunoreactive neurons and the numbers of TUNEL-positive cells in substantia nigra pars compacta ( SNpc) of PD mice. The protein expressions of Bax and cleaved caspase-3 were markedly down-regulated,whereas those of Bcl-2 and the ration of Bcl-2/Bax were significantly up-regulated by Cor pre-treatment followed by MPTP treatment. Furthermore, the protein expressions of p-p38 , p-ERK1/2 and p-JNK1/2 signif-icantly decreased in substantia nigra in Cor groups. Conclusions The results suggest that Cor can protect DA neurons against MPTP-induced injury by inhibiting apoptosis, which may be closely relevant to the inhibi-tion of MAPK signaling pathways.关键词
虫草素/MPTP/帕金森病/凋亡/多巴胺/MAPKKey words
cordycepin/MPTP/Parkinson 's dis-ease/apoptosis/dopamine/MAPK分类
医药卫生引用本文复制引用
樊逸云,唐培宸,顾欣霞,张鑫,孙莹,余伯成,张晓燕,葛晓群..虫草素对MPTP诱导的小鼠多巴胺能神经元损伤的保护作用及其机制[J].中国药理学通报,2018,34(6):797-803,7.基金项目
国家"十二五"863计划资助项目(No 2012AA021703) （No 2012AA021703）
扬州大学研究生科研创新计划项目( No XKYCX17067 ) （ No XKYCX17067 ）
扬州大学大学生学术科技创新基金项目(No x20170843) （No x20170843）
