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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 符文美 | |
| dc.contributor.author | Hsiao-Ching Yu | en |
| dc.contributor.author | 余曉青 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:30:23Z | - |
| dc.date.available | 2009-08-02 | |
| dc.date.copyright | 2006-08-02 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-20 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33232 | - |
| dc.description.abstract | 巴金森氏症是現今最常見的神經退化性疾病之一，在目前的醫療只能治標不能治本，並且對於其致病機轉仍然不清楚的情況下，研發新的治療藥物並研究致病原因是非常必要的。
我們發現YC-1可以減少SH-SY5Y受到MPP+和6-OHDA的損害，SH-SY5Y是神經母細胞瘤的細胞株，具有多巴胺神經的特徵，對MPP+和6-OHDA具有敏感性，而YC-1可以增加sGC對NO的感受性，是一個sGC 活化劑，早先被發現具有抗血小板凝集和使血管平滑肌放鬆的功能，之後又陸續有報告指出它在其他疾病模式下也有不同的效果。 YC-1可以抑制MPP+或6-OHDA造成SH-SY5Y細胞凋亡達50%以上，並且可以抑制MPP+或6-OHDA造成的Bcl-2 減少, PARP 斷裂, 以及procaspase-3 活化；我們認為YC-1並非藉由NO/cGMP/PKG訊息路徑達到神經保護的作用，因為給予NOS抑制劑(L-NAME, 7-NI)，sGC抑制劑(ODQ)，PKG抑制劑(KT 5823, RP-8-Br-PET-cGMPS)都不能有效抑制YC-1的作用；而且直接給予cGMP類似物(8-Br-cGMP)並無法減少MPP+和6-OHDA造成的細胞毒性，所以YC-1在這樣的實驗模式裡應該是透過其他路徑達到其神經保護的作用；此外，我們發現PKG抑制劑(KT 5823)可以保護SH-SY5Y細胞，降低MPP+或6-OHDA造成的細胞毒性，因此，我們認為PKG也許參與在MPP+或6-OHDA的毒性機轉當中，或者KT 5823有其他的作用標的。 綜合以上實驗結果，我們認為YC-1可以減少神經細胞受到MPP+或6-OHDA的傷害，有潛力發展成治療巴金森氏症的藥物，而它在細胞及動物模式的保護機轉則仍需再進一步探討。 | zh_TW |
| dc.description.abstract | Parkinson’s disease(PD) is one of the most common neurodegeneration diseases in the world and yet lacks a thorough cure. The studies on its pathogenesis as well as the development of new therapies are indispensable. A compound, YC-1, which was first reported to have an anti-platelet function, is found here to be neuroprotective in SH-SY5Y human neuroblastoma cell line. It can protect SH-SY5Y cells from the damage caused by MPP+ or 6-OHDA.
YC-1 inhibited MPP+ or 6-OHDA-induced cell death, which is evaluated by MTT reaction, PI flow cytometry, and DAPI staining. YC-1 also inhibited Bcl-2 degradation, PARP cleavage, and procaspase-3 activation caused by MPP+ or 6-OHDA. As a sGC activator, we then examined whether YC-1 protects SH-SY5Y through NO-cGMP-PKG pathway. However, all inhibitors acting in NO-cGMP-PKG pathway failed to suppress the effect of YC-1. The neuroprotective mechanism of YC-1 needs further investigation. On the contrary, the cell death induced by MPP+ or 6-OHDA was partially reversed by KT 5823, a PKG inhibitor, suggesting that PKG inhibition may be protective in dopaminergic neuronal cell line exposed to MPP+ or 6-OHDA. On the other hand, KT 5823 may also act on other targets except PKG. In conclusion, here we demonstrate that YC-1 possesses neuroprotective quality. Although the mechanisms of action of YC-1 in cell line and in animal model are still required to be investigated, YC-1 is likely to be a potential compound to treat PD patients. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:30:23Z (GMT). No. of bitstreams: 1 ntu-95-R93443016-1.pdf: 2462357 bytes, checksum: 9a65bd79045c6cd0195de493969dad95 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 縮寫表…………………………………………………………………1
英文摘要………………………………………………………………3 中文摘要………………………………………………………………4 緒論……………………………………………………………………6 實驗材料及方法………………………………………………………19 結果……………………………………………………………………24 討論……………………………………………………………………51 結論……………………………………………………………………61 參考文獻………………………………………………………………62 | |
| dc.language.iso | zh-TW | |
| dc.subject | 神經保護 | zh_TW |
| dc.subject | 巴金森氏症 | zh_TW |
| dc.subject | MPP+ | en |
| dc.subject | YC-1 | en |
| dc.subject | 6-OHDA | en |
| dc.subject | PKG | en |
| dc.subject | SH-SY5Y | en |
| dc.title | YC-1的神經保護作用機轉之探討 | zh_TW |
| dc.title | Studies on the neuroprotective effect of YC-1 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 顏茂雄,楊春茂,蘇銘嘉,湯志永 | |
| dc.subject.keyword | 神經保護,巴金森氏症, | zh_TW |
| dc.subject.keyword | YC-1,MPP+,6-OHDA,SH-SY5Y,PKG, | en |
| dc.relation.page | 70 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-21 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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