普拉克索贴剂对小鼠帕金森病模型的治疗作用研究

发布时间：2018-03-30 23:34

本文选题：普拉克索　切入点：贴剂　出处：《吉林大学》2017年硕士论文

【摘要】：帕金森病(Parkinson’s disease,PD)是中枢神经系统第二大神经退行性疾病,已成为中老年人健康的主要威胁。其主要病理学特点是多巴胺能神经元的选择性损伤,多巴胺(dopamine,DA)的减少和路易小体的形成。其潜在的发病机制与细胞凋亡、氧化应激、线粒体功能障碍、炎症反应和兴奋性毒性等有关。半衰期较短的药物每日须多次服药来维持药效,这对患者造成了很大的不便和较差的依从性。而且由于药物的消除使运动障碍复发时,PD患者进行简单的生活活动又将变得十分困难,峰谷现象带来的毒副作用也变得十分明显。基于以上问题,大连理工大学制药科学与技术学院将传统的盐酸普拉克索片剂改进为长效普拉克索贴剂,试图更好地发挥该新一代非麦角类多巴胺受体激动剂的作用。本实验探讨普拉克索贴剂对PD小鼠模型的治疗作用及其潜在作用机制,为其申报临床研究提供实验依据。本研究建立了1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导的小鼠PD模型,在贴剂治疗后进行了行为学测试、测量纹状体中DA及其代谢产物二羟基苯乙酸(Dihydroxy-phenyl aceticacid,DOPAC)和高香草酸(Homovanillic acid,HVA)的含量,并观察纹状体病理损伤、酪氨酸羟化酶(Tyrosine hydroxylase,TH)表达情况、氧化应激相关指标和细胞凋亡等,探讨普拉克索贴剂对小鼠PD模型的治疗作用及其机制。结果表明,普拉克索贴剂可以显著改善小鼠运动功能障碍,恢复多巴胺能神经元,增强抗氧化应激能力和抑制细胞凋亡。综上所述,普拉克索贴剂对小鼠PD模型具有良好治疗作用,其机制可能与抗氧化应激和抗凋亡相关。
[Abstract]:Parkinson's disease (PD) is the second largest neurodegenerative disease in the central nervous system (CNS) and has become a major threat to the health of the middle-aged and elderly.The main pathological features are selective injury of dopaminergic neurons, decrease of dopaminergic DAs and formation of Louie bodies.Its underlying pathogenesis is related to apoptosis, oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity.Drugs with shorter half-lives have to be taken multiple times a day to maintain their efficacy, which causes great inconvenience and poor compliance to patients.Because of the elimination of drugs, it will be very difficult for PD patients to carry out simple life activities when the motor disorders recur, and the toxic side effects brought by peak and valley phenomenon are also very obvious.Based on the above problems, the Institute of Pharmaceutical Science and Technology of Dalian University of Technology improved the traditional Praxol hydrochloride tablets into long-acting Praxol patches, in order to better play the role of the new generation of non-ergodic dopamine receptor agonists.The purpose of this study was to investigate the therapeutic effect of Praxol patch on PD mouse model and its potential mechanism, and to provide experimental evidence for clinical application.The pathological injury of striatum, the expression of tyrosine hydroxylase THH, the related indexes of oxidative stress and apoptosis were observed to explore the therapeutic effect and mechanism of Praxol patch on PD model in mice.The results showed that Praxol patch could significantly improve motor dysfunction, restore dopaminergic neurons, enhance antioxidant stress and inhibit apoptosis in mice.In conclusion, Praxol patch has a good therapeutic effect on PD model in mice, and its mechanism may be related to anti-oxidative stress and anti-apoptosis.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R965;R-332

【参考文献】