本文選題：普拉克索　切入點：貼劑　出處：《吉林大學》2017年碩士論文

【摘要】：帕金森病(Parkinson’s disease,PD)是中樞神經(jīng)系統(tǒng)第二大神經(jīng)退行性疾病,已成為中老年人健康的主要威脅。其主要病理學特點是多巴胺能神經(jīng)元的選擇性損傷,多巴胺(dopamine,DA)的減少和路易小體的形成。其潛在的發(fā)病機制與細胞凋亡、氧化應激、線粒體功能障礙、炎癥反應和興奮性毒性等有關。半衰期較短的藥物每日須多次服藥來維持藥效,這對患者造成了很大的不便和較差的依從性。而且由于藥物的消除使運動障礙復發(fā)時,PD患者進行簡單的生活活動又將變得十分困難,峰谷現(xiàn)象帶來的毒副作用也變得十分明顯。基于以上問題,大連理工大學制藥科學與技術(shù)學院將傳統(tǒng)的鹽酸普拉克索片劑改進為長效普拉克索貼劑,試圖更好地發(fā)揮該新一代非麥角類多巴胺受體激動劑的作用。本實驗探討普拉克索貼劑對PD小鼠模型的治療作用及其潛在作用機制,為其申報臨床研究提供實驗依據(jù)。本研究建立了1-甲基-4-苯基-1,2,3,6-四氫吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)誘導的小鼠PD模型,在貼劑治療后進行了行為學測試、測量紋狀體中DA及其代謝產(chǎn)物二羥基苯乙酸(Dihydroxy-phenyl aceticacid,DOPAC)和高香草酸(Homovanillic acid,HVA)的含量,并觀察紋狀體病理損傷、酪氨酸羥化酶(Tyrosine hydroxylase,TH)表達情況、氧化應激相關指標和細胞凋亡等,探討普拉克索貼劑對小鼠PD模型的治療作用及其機制。結(jié)果表明,普拉克索貼劑可以顯著改善小鼠運動功能障礙,恢復多巴胺能神經(jīng)元,增強抗氧化應激能力和抑制細胞凋亡。綜上所述,普拉克索貼劑對小鼠PD模型具有良好治療作用,其機制可能與抗氧化應激和抗凋亡相關。
[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.
【學位授予單位】：吉林大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R965;R-332

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本文編號：1688179