类叶升麻苷对MPTP所致帕金森病小鼠模型的神经保护作用

Neuroprotective effect of acteoside against MPTP-induced mouse model of Parkinsons disease

目的研究类叶升麻苷在MPTP诱导的C57小鼠的帕金森病(PD)模型中的神经保护作用及机制。方法通过自主活动实验和滚筒实验研究动物的行为表现,通过高效液相电化学检测方法观察脑纹状体多巴胺的变化,通过脑黑质酪氨酸羟化酶(tyroxinehydroxylase,TH)免疫组化染色观察多巴胺能神经元的损伤程度。并对黑质纹状体进行α-突触核蛋白(α-synuclein)的免疫印迹分析以探讨药物作用机制。结果①经MPTP诱导的C57小鼠,其自主活动次数、滚筒运动潜伏期均低于对照组(P<0·01);纹状体多巴胺含量明显降低(P<0·01);多巴胺能神经元数量明显减少;黑质纹状体α-synuclein蛋白水平下降。②经类叶升麻苷(10、30mg·kg-1)预处理后能明显改善MPTP诱导的C57小鼠的行为学表现,增加脑内多巴胺递质的含量,增加多巴胺能神经元的数量,增加黑质纹状体α-synuclein蛋白水平。结论类叶升麻苷具有神经保护作用,能对抗MPTP诱导的C57小鼠PD模型中的神经损伤。其机制可能与上调α-synuclein蛋白水平有关。

Aim To study the neuroprotective effect of Acteoside against MPTP-induced mouse model of Parkinsons disease （PD） and its mechanism. Methods The behavioral testing of C57 mice was assessed using spontaneous movement and rotarod test. DA levels in striatum were measured using HPLC-EC. Dopaminergic neurons in the substantia nigra were observed by immunohistochemical staining with an anti-Tyroxine hydroxylase （TH） antibody. Moreover, the mechanism of the neuroprotective effect of acteoside was investigated using Western blot analysis with an anti-α-synuctein antibody in the substantia nigra and striatum. Resuits （1） Compared with control, MPTP lesion significantly reduced the number of spontaneous movement and latent period of mice on the rotating rod （ both P 〈 0. 01 and DA levels in the striatum （P 〈0. 01 ）. Also there were less TH-immunoreactive signals in the substantia nigra, and α-synuclein levels in the substantia nigra and striatum were markedly decreased in MPTP- lesioned C57 mice. （2） Compared with MPTP model group, the number of spontaneous movement and latent period of mice on the rotating rod were significantly increased （ both P 〈 0. 01 ） and DA levels in striatum raised （P 〈0. 05 and P 〈0. 01 respectively） in acteoside-pretreated groups. Moreover, there were more TH-positive signals in the substantia nigra, and α-synuclein levels in the substantia nigra and striatum were significantly increased in MPTP-lesioned C57 mice pretreated with acteoside （30 mg·kg^-1 ）. Conclusions Acteoside may be able to protect C57 mice against MPTP-induced neuronal damage. The neuroprotective effect might be associated with the up-regulation of α- synuclein level.