注射用罗替戈汀微球延缓MPTP致神经元损伤作用探讨

Evaluation of Rotigotine Extended-Release Microspheres for Injection on Delaying MPTP-induced Neuronal Damage

本研究旨在通过模拟持续多巴胺能刺激(CDS)给药方式,评价注射用罗替戈汀缓释微球(Rotigotine Extended-release Microspheres for Injection,RoMS)对帕金森病(PD)小鼠神经元损伤的延缓作用.采用MPTP小鼠PD模型,并随机分为正常组、模型组、左旋多巴组、RoMS组、左旋多巴与RoMS联合给药组,在给药期间进行行为学检测,给药结束后,分析各给药组对氧化应激相关蛋白nNOS、Cyt-C及黑质酪氨酸羟化酶(TH)表达水平的影响.结果表明,RoMS和联合用药组可明显延长小鼠转棒、悬尾、强迫游泳时间,下调黑质中nNOS、Cyt-C的含量,增加TH神经元的表达.本研究说明,RoMS具有抗氧化应激,减轻多巴胺神经元损伤,改善运动障碍的作用,并且在联用低剂量L-DOPA时,可同时发挥协同增效和神经保护作用.

The neuroprotective effect of Rotigotine Extended-release Microspheres for Injection(RoMS)is investigated by simulating continuous dopaminergic stimulation(CDS).C57BL/6 male mice are injected with MPTP to establish a mouse PD model.Then,the mice are administered with CMC-Na,levodopa(L-DOPA),RoMS,L-DOPA+RoMS respectively and behavior tests are performed during the administration.The oxidative stress-related proteins nNos,Cyt-C and the numbers of tyrosine hydroxylase(TH)positive neurons are detected after the last dose.The results show that RoMS and combination group can significantly prolong the time of rotation,tail suspension,swimming,down-regulate the content of nNOS,Cyt-C in the substantia nigra and increase the expression of TH in neurons.In conclusion,RoMS can reduce oxidative stress,alleviate neuronal damage,improve dyskinesia,and when combined with low-dose L-DOPA,synergistic and neuroprotective effects can be simultaneously exerted.