建立符合藥物研發需求之帕金森疾病小鼠模式

Establishment of A Mice Model with Parkinson's Disease Suitable for the Need of Research and Development of Drugs

李卓臨(Cho-Lin Li) ； 陳嘉琪(Chia-Chi Chen) ； 紀子云(Tzu-Yun Chi) ； 邱健昭(Chien-Chao Chiu) ； 林家羽(Chia-Yu Lin) ； 洪瑛璟(Ying-Ching Hung) ； 陳筱云(Hsiao-Yun Chen) ； 洪紹文(Shao-Wen Hung)

《嘉大農林學報》 17卷2期 (2020/09) Pp. 13-32

摘要

帕金森氏症（Parkinson s disease，PD）是最常見的神經退行性疾病之一，導致此運動功能不足的原因，是因為腦中產生多巴胺（dopamine）的神經細胞退化或死亡，目前沒有藥物可以完全治癒PD。本研究利用MPTP（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine）來誘發產生PD小鼠，並將PD小鼠隨機分成2組Selegiline組與陰性對照組。此外，正常組不以MPTP進行誘發PD。利用市售ELISA檢測套組與HPLC（high performance liquid chromatography）檢測小鼠大腦紋狀體多巴胺含量、抗氧化能力指標﹝catalase、G6PDH（glucose-6-phosphate dehydrogenase）、SOD（superoxide dismutase）﹞、抗老化生物活性指標﹝8-OH-dG（8-hydroxy-2-deoxyguanosine）、protein carbonyl content、MDA（malondialdehyde）content﹞及黑質緻密部（subtantia nigra pars compacta，SNpc）tyrosine hydroxylase（TH）抗原表現。結果可見Selegiline組與正常組的大腦紋狀體的多巴胺表現，皆顯著高於陰性對照組；Selegiline組與正常組的腦組織與血清中的3種抗老化生物活性指標表現，皆顯著低於陰性對照組；Selegiline組與正常組的腦內與老化相關的抗氧化能力指標表現，皆顯著高於陰性對照組；Selegiline組與正常組在黑質緻密部TH抗原染色陽性神經元顯著高於陰性對照組。由結果得知，本研究已成功建立了PD小鼠模式和藥物篩選系統，未來可藉由此動物模式，提供PD藥物治療策略開發。

關鍵字

老化 ； 藥物篩選 ； 多巴胺 ； 指標 ； 帕金森氏症小鼠

並列摘要

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The cause of this lack of motor function is due to the degeneration or death of dopamine-producing neurons in the brain. Currently, there are no drugs that can completely cure PD. In this study, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was used for inducing the PD mice. These PD mice were randomly divided into the two Selegiline-treated groups and the negative control group. In addition, the normal control group did not induce PD with MPTP. Using commercially available ELISA kits and high performance liquid chromatography to detect dopamine content in brain striatum, antioxidant ability index [Catalase, G6PDH (glucose-6-phosphate dehydrogenase), SOD (Superoxide dismutase)], anti-aging biological activity index [8-OH-dG (8-hydroxy-2- deoxyguanosine), Protein carbonyl content, MDA (Malondialdehyde) content] and tyrosine hydoxylase (TH) expression in the substantia nigra pars compacta. The results showed that the dopamine performance of the striatum was significantly higher in the selegiline-treated groups and the normal control group than that in the negative control group; the anti-aging biological activity index in brain tissue and serum were significantly lower in the selegiline-treated groups and the normal control group than those in the negative control group; the antioxidant ability index in the brain were significantly higher in the selegiline-treated groups and the normal group than those in the negative control group; the TH antigen-positive neurons in the substantia nigra pars compacta were significantly higher in the selegiline-treated groups and the normal control group than those in the negative control group. It is known from the results that a mouse PD model and drug screening systems have been successfully established in this study. In the future, this animal model will be used for the research and development on PD drug screening and therapeutic strategies.

並列關鍵字

Aging ； Drug screening ； Dopamine ； Industry need ； Indicators ； Mouse model with Parkinson's disease