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題名 探討厚朴對神經毒素引起的神經傷害及行為異常之保護與治療效用
Evaluation of the protective and therapeutic effects of cortex Magnoliae on neuronal damage and abnormal behavior induced by neurotoxins
作者 廖筱玉
貢獻者 詹銘煥
廖筱玉
關鍵詞 厚朴
百草枯
MPTP
認知功能障礙
神經保護
Cortex Magnoliae
paraquat
MPTP
cognitive impairment
neuroprotection
日期 2013
上傳時間 1-May-2014 15:21:46 (UTC+8)
摘要 中文摘要
     厚朴，採用厚朴植物之樹皮，是ㄧ種已知可應用於治療精神疾病的傳統天然藥物，例如：憂鬱症等。厚朴主要的有效多酚環成分已被證實具有抗氧化、抗發炎及抗興奮性毒殺等神經保護作用，因此，推測厚朴可作為一種潛在治療像是帕金森氏症這累神經退化性疾病之藥物。本研究之目的為探討厚朴是否可以預防與治療因百草枯及MPTP所誘導的毒害及學習、記憶和運動功能缺失等行為異常現象。本研究監測Oregon-R品系之果蠅(年齡：1-2, 20天或30天)之壽命在長期暴露於百草枯(5-20 mM)並先給予厚朴(100, 300或600 mg/L)治療之變化。其結果顯示，厚朴無法延長暴露在百草枯環境下之果蠅壽命。另外，我們給予雄性ICR小鼠(30-35 g)，連續五天，每日一劑MPTP(25 mg/kg, i.p.)，誘導神經毒性及行為異常現象。在共同投藥組別，在給予MPTP注射前一小時，先以灌餵方式給予小鼠厚朴(100或300 mg/kg)預防，連續五天後，只單獨給予厚朴治療連續十四天。後投藥組別，在給予最後一劑MPTP後，連續十四天給予厚朴(100或300 mg/kg).治療。在控制組別中，給予生理食鹽水(0.9%, i.p.)及灌餵玉米油。結果顯示，MPTP與厚朴並不影響小鼠之運動協調功能，然而，可利用新位置辨識能力測試及新物體辨識認知行為測試，檢測因MPTP所引起之認知功能障礙現象，由我們結果中顯示，不論是與MPTP共同給予厚朴治療抑或是後處理厚朴皆可恢復因MPTP所造成的認知功能障礙現象，此外，厚朴也可恢復因MPTP所造成多巴胺神經元及多巴胺轉運子受損之情形，另外，我們也初步發現，厚朴可在海馬迴中使Nrf2表現量提升。因此，初步結果表明，厚朴將可成為未來治療帕金森氏症之天然藥物。
Cortex Magnoliae, the bark of Magnolia officinalis, has been prescribed in the traditional herbal medicine to treat a variety of mental disorders including depression. The main constituents of cortex Magnoliae contain the biphenyl compounds such as honokiol and magnolol. Both biphenyl compounds were shown to have the neuronal protective effect which is related to the anti-oxidation, anti-inflammation, and anti-excitatory toxicity. Thus, it was proposed that cortex Magnoliae may act as the potential therapeutic agent for the treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether cortex Magnoliae exhibits the neuroprotective and therapeutic action against the neuronal toxicity and behavioral deficits in learning, memory, and motor function induced by neurotoxin paraquat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in PD-like models. The lifespan of flies from Oregon-R strain of Drosophila melanogaster (age: 1-2, 20 or 30 days) chronically exposed to paraquat (5-20 mM) with pre-treatment of Cortex Magnoliae (100, 300 or 600 mg/L) were measured. Results showed that pre-treatment of Cortex Magnoliae could not extend the lifespan of the flies reduced by paraquat. On the other hand, male ICR mice (30-35g) were administered with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neurotoxicity and behavioral impairment. In co-treatment group, male mice were orally administrated with cortex Magnoliae (100 or 300 mg/kg) 1 hour before MPTP injection for 5 days and then followed by oral administration of cortex Magnoliae alone for consecutive 14 days. Mice in post-treatment group were orally administered with cortex Magnoliae (100 or 300 mg/kg) for consecutive 14 days after the final injection of MPTP. Mice in control group were injected with saline (0.9%, i.p.) and orally administrated with vehicle (corn oil). Our results showed that MPTP and cortex Magnoliae did not affect mouse coordination and balance in beam walking test. However, cortex Magnoliae improved the cognitive impairments determined by novel-location recognition task (NLRT) and novel-object recognition task (NORT) in MPTP-induced PD mouse. Additionally, cortex Magnoliae restored MPTP-induced loss of dopaminergic neurons and recovered MPTP-induced loss of dopamine transporters in striatum. Cortex Magnoliae also activated Nrf2 in hippocampus. Therefore, the preliminary results suggest that cortex Magnoliae may be a novel candidate for the treatment of Parkinson`s disease in the future. The pharmacological mechanism of cortex Magnoliae in PD treatment needs further study.
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描述 碩士
國立政治大學
神經科學研究所
100754005
102
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0100754005
資料類型 thesis
dc.contributor.advisor 詹銘煥zh_TW
dc.contributor.author (Authors) 廖筱玉zh_TW
dc.creator (作者) 廖筱玉zh_TW
dc.date (日期) 2013en_US
dc.date.accessioned 1-May-2014 15:21:46 (UTC+8)-
dc.date.available 1-May-2014 15:21:46 (UTC+8)-
dc.date.issued (上傳時間) 1-May-2014 15:21:46 (UTC+8)-
dc.identifier (Other Identifiers) G0100754005en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/65776-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 神經科學研究所zh_TW
dc.description (描述) 100754005zh_TW
dc.description (描述) 102zh_TW
dc.description.abstract (摘要) 中文摘要
     厚朴，採用厚朴植物之樹皮，是ㄧ種已知可應用於治療精神疾病的傳統天然藥物，例如：憂鬱症等。厚朴主要的有效多酚環成分已被證實具有抗氧化、抗發炎及抗興奮性毒殺等神經保護作用，因此，推測厚朴可作為一種潛在治療像是帕金森氏症這累神經退化性疾病之藥物。本研究之目的為探討厚朴是否可以預防與治療因百草枯及MPTP所誘導的毒害及學習、記憶和運動功能缺失等行為異常現象。本研究監測Oregon-R品系之果蠅(年齡：1-2, 20天或30天)之壽命在長期暴露於百草枯(5-20 mM)並先給予厚朴(100, 300或600 mg/L)治療之變化。其結果顯示，厚朴無法延長暴露在百草枯環境下之果蠅壽命。另外，我們給予雄性ICR小鼠(30-35 g)，連續五天，每日一劑MPTP(25 mg/kg, i.p.)，誘導神經毒性及行為異常現象。在共同投藥組別，在給予MPTP注射前一小時，先以灌餵方式給予小鼠厚朴(100或300 mg/kg)預防，連續五天後，只單獨給予厚朴治療連續十四天。後投藥組別，在給予最後一劑MPTP後，連續十四天給予厚朴(100或300 mg/kg).治療。在控制組別中，給予生理食鹽水(0.9%, i.p.)及灌餵玉米油。結果顯示，MPTP與厚朴並不影響小鼠之運動協調功能，然而，可利用新位置辨識能力測試及新物體辨識認知行為測試，檢測因MPTP所引起之認知功能障礙現象，由我們結果中顯示，不論是與MPTP共同給予厚朴治療抑或是後處理厚朴皆可恢復因MPTP所造成的認知功能障礙現象，此外，厚朴也可恢復因MPTP所造成多巴胺神經元及多巴胺轉運子受損之情形，另外，我們也初步發現，厚朴可在海馬迴中使Nrf2表現量提升。因此，初步結果表明，厚朴將可成為未來治療帕金森氏症之天然藥物。		zh_TW
dc.description.abstract (摘要) Cortex Magnoliae, the bark of Magnolia officinalis, has been prescribed in the traditional herbal medicine to treat a variety of mental disorders including depression. The main constituents of cortex Magnoliae contain the biphenyl compounds such as honokiol and magnolol. Both biphenyl compounds were shown to have the neuronal protective effect which is related to the anti-oxidation, anti-inflammation, and anti-excitatory toxicity. Thus, it was proposed that cortex Magnoliae may act as the potential therapeutic agent for the treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether cortex Magnoliae exhibits the neuroprotective and therapeutic action against the neuronal toxicity and behavioral deficits in learning, memory, and motor function induced by neurotoxin paraquat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in PD-like models. The lifespan of flies from Oregon-R strain of Drosophila melanogaster (age: 1-2, 20 or 30 days) chronically exposed to paraquat (5-20 mM) with pre-treatment of Cortex Magnoliae (100, 300 or 600 mg/L) were measured. Results showed that pre-treatment of Cortex Magnoliae could not extend the lifespan of the flies reduced by paraquat. On the other hand, male ICR mice (30-35g) were administered with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neurotoxicity and behavioral impairment. In co-treatment group, male mice were orally administrated with cortex Magnoliae (100 or 300 mg/kg) 1 hour before MPTP injection for 5 days and then followed by oral administration of cortex Magnoliae alone for consecutive 14 days. Mice in post-treatment group were orally administered with cortex Magnoliae (100 or 300 mg/kg) for consecutive 14 days after the final injection of MPTP. Mice in control group were injected with saline (0.9%, i.p.) and orally administrated with vehicle (corn oil). Our results showed that MPTP and cortex Magnoliae did not affect mouse coordination and balance in beam walking test. However, cortex Magnoliae improved the cognitive impairments determined by novel-location recognition task (NLRT) and novel-object recognition task (NORT) in MPTP-induced PD mouse. Additionally, cortex Magnoliae restored MPTP-induced loss of dopaminergic neurons and recovered MPTP-induced loss of dopamine transporters in striatum. Cortex Magnoliae also activated Nrf2 in hippocampus. Therefore, the preliminary results suggest that cortex Magnoliae may be a novel candidate for the treatment of Parkinson`s disease in the future. The pharmacological mechanism of cortex Magnoliae in PD treatment needs further study.en_US
dc.description.tableofcontents 圖表目錄 3
     縮寫表 5
     壹、背景介紹 6
      一、前言 6
      二、帕金森氏症 7
      三、帕金森氏症病理學特徵 9
      四、帕金森氏症的致病機轉 10
      五、酪胺酸羥化酶在帕金森氏症的角色 13
      六、多巴胺轉運子在帕金森氏症的角色 13
      七、膠質纖維酸性蛋白在帕金森氏症的角色 13
      八、氧化壓力與帕金森氏症的相關性 13
      九、Nrf2在帕金森氏症的角色 14
      十、帕金森氏症的治療 15
      十一、厚朴 18
      十二、引發帕金森氏症的動物模式 20
     貳、實驗動機與目的 24
     參、實驗材料與方法 25
     肆、實驗結果 37
     伍、討論 42
     陸、結論 46
     柒、圖表 47
     捌、參考文獻 64		zh_TW
dc.language.iso en_US-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0100754005en_US
dc.subject (關鍵詞) 厚朴zh_TW
dc.subject (關鍵詞) 百草枯zh_TW
dc.subject (關鍵詞) MPTPzh_TW
dc.subject (關鍵詞) 認知功能障礙zh_TW
dc.subject (關鍵詞) 神經保護zh_TW
dc.subject (關鍵詞) Cortex Magnoliaeen_US
dc.subject (關鍵詞) paraquaten_US
dc.subject (關鍵詞) MPTPen_US
dc.subject (關鍵詞) cognitive impairmenten_US
dc.subject (關鍵詞) neuroprotectionen_US
dc.title (題名) 探討厚朴對神經毒素引起的神經傷害及行為異常之保護與治療效用zh_TW
dc.title (題名) Evaluation of the protective and therapeutic effects of cortex Magnoliae on neuronal damage and abnormal behavior induced by neurotoxinsen_US
dc.type (資料類型) thesisen
dc.relation.reference (參考文獻) 捌、參考文獻
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