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

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
樊逸云;唐培宸;顾欣霞;张鑫;孙莹;余伯成;张晓燕;葛晓群
【期刊名称】《中国药理学通报》
【年(卷),期】2018(34)6
【摘要】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.%目的观察虫草素(Cor)对MPTP诱导的帕金森病(PD)小鼠多巴胺(DA)能神经元的保护作用,并探讨其可能的机制.方法以MPTP制备PD小鼠模型,Cor(2.5、5.0、10.0 mg·kg-1)预处理灌胃给药.旷场、转棒和爬杆实验检测小鼠的运动能力;HPLC-ECD法、免疫组织化学法和TUNEL法分别检测DA含量、TH阳性细胞数和凋亡细胞;Western blot法检测凋亡相关蛋白和MAPK信号通路相关蛋白的表达.结果 Cor能明显改善PD小鼠的运动功能障碍,提高纹状体DA、DOPAC、HVA含量,减轻黑质TH免疫阳性神经元的丢失,并减少凋亡细胞数.另一方面,Cor可明显下调PD小鼠黑质中Bax和Cleaved caspase-3蛋白表达水平,增加Bcl-2蛋白表达及Bcl-2/Bax的比值.同时,Cor能明显下调黑质p-p38、p-ERK1/2、p-JNK1/2蛋白的表达.结论Cor对MPTP诱导的PD小鼠DA能神经元具有保护作用,其机制可能是通过抑制MAPK信号通路的激活,抑制DA能神经元凋亡.
【总页数】7页(P797-803)
【作者】樊逸云;唐培宸;顾欣霞;张鑫;孙莹;余伯成;张晓燕;葛晓群
【作者单位】扬州大学医学院药理学教研室,江苏扬州 225001;上海国宝企业发展中心,上海 201203;扬州大学医学院药理学教研室,江苏扬州 225001;上海国宝企业发展中心,上海 201203;扬州大学医学院药理学教研室,江苏扬州 225001;上海国宝企业发展中心,上海 201203;扬州大学医学院药理学教研室,江苏扬州 225001;扬州大学医学院药理学教研室,江苏扬州 225001
【正文语种】中文
【中图分类】R-332;R284.1;R322.81;R329.25;R742.5;R745.7;R977.6
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