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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 沈立言 | |
| dc.contributor.author | Huei-Ying Lin | en |
| dc.contributor.author | 林惠瑩 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:53:45Z | - |
| dc.date.available | 2010-08-06 | |
| dc.date.copyright | 2010-08-06 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-30 | |
| dc.identifier.citation | 行政院衛生署。2009。民國97年主要死因分析。
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46094 | - |
| dc.description.abstract | 根據行政院衛生署公告之死因統計，歷年(1987~2008年)來自殺之死亡人數有逐年攀升之趨勢，而世界衛生組織也指出，自殺的人當中高達80-100%的人有精神疾病，又以憂鬱症患者居多。已有研究指出憂鬱症的患者多有hypothalamic-pituitary-adrenal axis (HPA axis)過度活化的情形，進而會引起醣皮質固醇(glucocorticoids，如皮質固酮corticosterone, Cort)過度分泌與興奮性胺基酸(excitatory amino acid, EAA，如glutamate)之積聚，結果造成鈣離子通道過度被活化而致使細胞內鈣離子濃度過高，若大量的鈣離子積聚於粒線體內，粒線體膜通透性會因此發生改變，促細胞凋亡因子尌被釋出至細胞質，最終誘使神經細胞走向細胞凋亡，而這些神經細胞的減少可能與憂鬱症有關。天麻為傳統中藥材，已有研究指出天麻具有抗抽搐、抗氧化等生理活性。本實驗室之前的研究也證實天麻水萃物(water extract of Gastrodia elata Bl., WEGE)具有抗憂鬱功效，其對老鼠腻中單胺類神經傳導物質的調節為其可能機制之一。因此，本研究之目的乃藉由Cort誘導rat adrenal pheochromocytoma PC12細胞損傷之神經毒性(neurotoxicity)，探討WEGE與可能活性成分對Cort所造成PC12細胞損傷之保護作用，於細胞模式中瞭解WEGE抗憂鬱之可能作用機制。研究結果顯示，4-hydroxybenzyl alcohol (HBA)可能為WEGE抗憂鬱活性成分之一。WEGE與HBA皆能顯著抑制由Cort誘導所造成PC12細胞存活率之下降，sub-G1期比例之增加，細胞內鈣離子濃度之上升，以及caspase-3的活性之增加。此外，WEGE和HBA亦會調節細胞凋亡相關蛋白質之表現，包括抑制由Cort誘導所造成之促凋亡Bax蛋白質表現量之增加、抑凋亡Bcl-2蛋白質表現量之減少，以及pro-caspase-9蛋白質表現量之減少和裂解態PARP蛋白質表現量之增加。由上述結果得知WEGE與HBA可保護PC12細胞免於Cort引起細胞內鈣離子濃度增加所造成之細胞凋亡，故推測天麻水萃物之抗憂鬱能力可能與減少憂鬱症相關神經元細胞的損傷有關。 | zh_TW |
| dc.description.abstract | According to the report of department of Health, Executive Yuan, the event of suicide-caused death is getting more from 1987 to 2008. WHO reported that 80-100% of suicided people are the patients with mental disorder, especially depression. Most patients with depression had the hyperactivity of hypothalamic-pituitary-adrenal axis (HPA axis) which induces over-excretion of glucocorticoids such as corticosterone (Cort) and accumulation of excitatory amino acids (EAA) such as glutamate, and then results in high activation of calcium channel and overloading of intracellular calcium. Accumulated calcium ions in mitochondrial change mitochondrial membrane permeability and release apoptosis-related factors to cytosol to induce cell death via apoptosis. The loss of neuron cells is related to depression. Gastrodia elata Bl., a traditional Chinese medicine, exhibits lots of bioactivities, including anticonvulsion, antioxidation, etc. Our previous study demonstrated that water extract of Gastrodia elata Bl. (WEGE) has an antidepressive effect and an ability to modulate the amounts of monoamines in the rat brain. In the present study, neuroprotective effect of WEGE and possible active compounds on the Cort-induced lesion in PC12 cells was investigated to understand the antidepression mechanism of WEGE. The result of HPLC analysis indicated that 4-hydroxybenzyl alcohol (HBA) might be one of the potential active compounds with antidepressive ability in WEGE. Both of WEGE and HBA inhibited the Cort-induced decrease of cell viability and increase of percentage of sub-G1, concentration of intracellular calcium, and activity of caspase-3. Additionally, WEGE and HBA inhibited the Cort-induced increase of pro-apoptotic Bax and cleaved PARP protein expression, while they also maintained the decrease of anti-apoptotic Bcl-2 and pro-caspase-9 protein expression those caused by Cort in PC12 cells. Therefore, WEGE and HBA protected PC12 cells from the cort-induced apoptosis accompanied with increased the intracellular calcium concentration, and it suggested that one of the
depression mechanism of WEGE is to decrease the loss of neuron cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:53:45Z (GMT). No. of bitstreams: 1 ntu-99-R97641030-1.pdf: 2148522 bytes, checksum: 84ea26a9adce3443482d48c9d36d1378 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 目錄
中文摘要 ....................................... I 英文摘要 ......................................... II 目錄 ..................................... IV 圖次 ........................................ VII 表次 .................................... IX 第一章 前言 ....................................... 1 第二章 文獻回顧 ................................ 2 第一節、憂鬱症 ...................................2 一、憂鬱症之簡介 ......................... 2 二、憂鬱症之診斷及其症狀 ......................... 4 三、憂鬱症之病因 ........................... 5 四、憂鬱症之治療 ................................. 9 第二節、天麻 ................................. 11 一、簡介 ...................................... 11 二、活性成分 ................................. 11 三、生理活性 ................................. 11 第三節、憂鬱症細胞模式 ..........................17 一、PC12細胞 .................................... 17 二、下視丘-腻下垂體-腎上腺軸(hypothalamus-pituitary-adrenal axis, HPA axis) ................................ 19 三、細胞內鈣離子濃度與細胞凋亡 ..................... 22 第三章 研究目的 .................................. 24 第四章 實驗架構 .................................. 24 第五章 材料與方法 ............................... 25 第一節、實驗材料與儀器設備 ........................25 一、實驗材料 ..................................... 25 二、實驗藥品 .................................... 25 三、儀器設備 .................................... 26 四、實驗細胞株 ................................. 27 第二節、實驗方法 ...........................28 一、天麻水萃物及其活性成分對皮質固酮造成PC12細胞之損傷的保護效應 ............................ 28 二、天麻水萃物活性成分分析 ......................... 31 三、天麻水萃物及其活性成分對皮質固酮誘導PC12細胞之細胞凋亡相關蛋白質表現的影響 ............................... 32 四、統計分析 ................................... 33 第六章 實驗結果 ................................ 34 一、天麻水萃物(water extract of Gastrodia elata Bl., WEGE)對皮質固醇 (corticosterone, Cort)造成PC12細胞之損傷的保護效應 ........................... 34 二、天麻可能活性成分對Cort造成PC12細胞之損傷的保護效應 .. 35 三、WEGE與其可能活性成分對Cort造成PC12細胞形態改變之影響 37 四、WEGE可能活性成分之分析 ....................... 38 五、WEGE與其活性成分對Cort誘導PC12細胞之細胞凋亡相關蛋白質表現的影響 .................................... 38 第七章 討論 ...................................... 55 一、天麻水萃物(water extract of Gastrodia elata Bl., WEGE)對Cort造成PC12細胞之損傷的保護效應 .................. 55 二、天麻可能活性成分對Cort造成PC12細胞之損傷的保護效應 .. 57 三、WEGE與其可能活性成分對Cort造成PC12細胞形態改變之影響 58 四、WEGE活性成分分析 .............................. 59 五、WEGE與其活性成分HBA對Cort誘導PC12細胞之細胞凋亡相關蛋 白質表現的影響 ................................. 60 第八章 結論及未來研究方向 ....................... 63 第九章 參考文獻 .................... 64 附錄 ............................................... 72 圖次 圖一、歷年自殺死亡數及死亡占率 ....................3 圖二、突觸末端之多巴胺、正腎上腺素以及血清素 .......7 圖三、神經突觸 ..................................8 圖四、vanillin、HB以及HBA之化學結構 ..............15 圖五、天麻素以及HBA之化學結構 ....................16 圖六、下視丘-腻下垂體-腎上腺軸 ...................19 圖七、麩胺酸受體以及突觸可塑性 .....................21 圖八、粒線體之凋亡路徑 ........................23 圖九、不同濃度之天麻水萃物對PC12細胞存活率之影響....40 圖十、天麻水萃物對皮質固酮造成PC12細胞之損傷的保護效應....41 圖十一、天麻水萃物對皮質固酮造成PC12細胞內鈣離子濃度過度負載的影響 ......................................42 圖十二、天麻水萃物對皮質固酮造成PC12細胞之caspase-3活性改變的影響 ......................................43 圖十三、天麻水萃物對皮質固酮誘導PC12細胞sub-G1期增加之抑制效應 ..44 圖十四、Vanillin (VAN) (A)、4-hydroxybenzaldehyde (HB) (B)以及4-hydroxybenzyl alcohol (HBA) (C)對皮質固酮造成PC12細胞之損傷的保護效應 .................................46 圖十五、Vanillin (VAN)、4-hydroxybenzaldehyde (HB)以及4-hydroxybenzyl alcohol (HBA)對皮質固酮造成PC12細胞之細胞內鈣離子濃度過度負載的影響 ........................47 圖十六、Vanillin (VAN)、4-hydroxybenzaldehyde (HB)以及4-hydroxybenzyl alcohol (HBA)對皮質固酮造成PC12細胞之caspase-3活性的影響 ..................48 圖十七、Vanillin (VAN)、4-hydroxybenzaldehyde (HB)以及4-hydroxybenzyl alcohol (HBA)對皮質固酮造成PC12細胞之sub-G1期增加之抑制效應 ..........49 圖十八、天麻水萃物以及Vanillin (VAN)、4-hydroxybenzaldehyde (HB) 4-hydroxybenzyl alcohol (HBA)對皮質固酮造成PC12細胞形態改變之影響 ...50 圖十九、標準品(A)，天麻水萃物(B)，以及經beta-葡萄糖苷酵素水解後之天麻水萃物(C)的HPLC分析圖譜 ...............51 圖二十、天麻水萃物以及其活性成分4-hydroxybenzyl alcohol (HBA)對皮質固酮誘導PC12細胞之細胞凋亡相關蛋白質表現的影響..53 圖二十一、天麻水萃物以及其活性成分4-hydroxybenzyl alcohol (HBA)對皮質固酮誘導PC12細胞內caspase-9和PARP蛋白質之影響 .54 表次 表一、世界十大高負擔疾病2004年排名與2030年預估排名 .4 表二、大鼠腎上腺髓質嗜鉻細胞瘤細胞與正常相似細胞之比較 ..18 表三、Vanillin (VAN)、4-hydroxybenzaldehyde (HB)以及4-hydroxybenzyl alcohol (HBA)對PC12細胞存活率之影響 .......45 表四、天麻水萃物中Vanillin (VAN)、4-hydroxybenzaldehyde (HB)與 4-hydroxybenzyl alcohol (HBA)的濃度 .................52 | |
| dc.language.iso | zh-TW | |
| dc.subject | 憂鬱症 | zh_TW |
| dc.subject | PC12細胞 | zh_TW |
| dc.subject | 鈣離子 | zh_TW |
| dc.subject | 天麻 | zh_TW |
| dc.subject | 皮質固酮 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | apoptosis | en |
| dc.subject | PC12 cells | en |
| dc.subject | corticosterone | en |
| dc.subject | Gastrodia elata Bl. | en |
| dc.subject | depression | en |
| dc.subject | calcium | en |
| dc.title | 天麻水萃物對皮質固酮誘導PC12細胞損傷之神經保護功效 | zh_TW |
| dc.title | Neuroprotective effect of water extract of Gastrodia
elata Bl. on the corticosterone-induced lesion in rat adrenal pheochromocytoma PC12 cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 潘建源,謝慶良,黃士懿,朱有田 | |
| dc.subject.keyword | 憂鬱症,天麻,皮質固酮,PC12細胞,鈣離子,細胞凋亡, | zh_TW |
| dc.subject.keyword | depression,Gastrodia elata Bl.,corticosterone,PC12 cells,calcium,apoptosis, | en |
| dc.relation.page | 88 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-07-30 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 食品科技研究所 | zh_TW |
| 顯示於系所單位： | 食品科技研究所 | |
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