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博碩士論文 etd-0804110-105556 詳細資訊
Title page for etd-0804110-105556
論文名稱
Title
右美沙芬對於斑馬魚骨頭生成之影響
The Effects of Dextromethorphan on Bone Formation in Zebrafish
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
79
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2010-03-05
繳交日期
Date of Submission
2010-08-04
關鍵字
Keywords
細胞外信號調節酶 (ERK)、熱休克蛋白 (Hsp)、NMDA 接受器、右美沙芬、麩胺酸、斑馬魚胚胎
dextromethorphan, phospho-ERK, Hsp90, Hsp25, zebrafish embryo, NMDA receptor, glutamate
統計
Statistics
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中文摘要
斑馬魚 (Danio rerio) 在研究發育上相較於其他物種而言擁有諸多優越性並已成為重要之模式,其中包括 (1) 胚胎容易取得並可直接觀察其發育過程,以及 (2) 適合進行基因系統之研究,以調查突變的基因調節與各種組織與器官之發育,以及骨骼系統。近年來,麩氨酸 (glutamate) 接受器被證實存在於許多形式之骨細胞中,同時調節骨頭之生理功能。在本研究中,我們利用Calcein 染色探討有關NMDA 接受器非競爭型拮抗劑,右美沙芬 (dextromethorphan) 對於斑馬魚胚胎時期中軸骨架 (axial skeleton) 發育之影響。實驗數據顯示,麩氨酸顯著減緩右美沙芬抑制中軸骨架的形成。此外,免疫螢光染色結果也說明,NMDA 接受器之次單位體NR1 確實於胚胎中軸骨架部位表現。另一方面,右美沙芬抑制中軸骨頭之生長,也會影響熱休克蛋白 (Heat shock protein, Hsp) 與細胞外信號調節酶 (Extracellular signal-regulated kinases, ERK) 之表現。因此,我們認為NMDA 接受器在中軸骨架之發育過程,扮演非常重要之角色。不過,對於麩氨酸在骨頭形成之細胞機轉過程扮演何種角色,仍需進一步的探討。
Abstract
Zebrafish, Danio rerio, have become an important model for developmental studies and have several advantages over other model systems. These advantages include (1) the easy accessibility of zebrafish embryos for direct observation of their development and (2) their suitability for systematic mutagenesis studies for the identification of genes regulating the development of various tissues and organs, including the skeletal system. Recently, it has been reported that glutamate receptors are expressed in many types of bone cells and regulate bone physiological functions. In the present study, we have examined the effects of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist—dextromethorphan—on the development of the axial skeleton in zebrafish embryos by using calcein stain. Our results revealed that dextromethorphan significantly attenuates the formation of the axial skeleton and that it is inhibited on pretreatment with glutamate. Moreover, immunohistochemical analysis revealed protein level expression of the NMDA subunit NR1 in the axial region of zebrafish. Our results also indicate that attenuation of NMDA receptor activity-induced change in the axial skeleton may be related to heat-shock protein and extracellular signal-regulated kinase (ERK) signalings. In conclusion, we suggest that the NMDA receptor plays an important role in the development of the axial skeleton. However, further studies are required on the cellular mechanisms of glutamate regulated bone formation.
目次 Table of Contents
謝誌............................................................... I
目錄..............................................................III
圖目錄..........................................................VI
中文摘要.......................................................VIII
Abstract..........................................................IX

第一章 文獻回顧
(一) 前言.......................................................... 1
(二) 右美沙芬...................................................... 2
(三) 麩胺酸接受器之種類............................................ 3
(四) 骨頭形成機制...................................................4
(五) 麩胺酸接受器於成骨細胞中扮演之角色............................ 5
(六) NMDA 接受器於成骨細胞中扮演之角色............................ 6
(七) ERK 訊息路徑對於骨頭發育時期之影響.............................8
(八) 熱休克蛋白質於骨頭發育時期之角色............................. 9
(九) 研究目標......................................................11

第二章 研究方法及步驟
(一) 種魚飼養......................................................13
(二) 胚胎獲得..................................................... 13
(三) 全覆式免疫組織化學染色法.. ...................................13
(四) 藥物處理..................................................... 14
(五) 胚胎型態觀察................................................. 15
(六) 以Calcein 染色觀察稚魚骨頭發育................................ 15
(七) 西方點墨法.................................................... 15
(八) 統計方式......................................................17

第三章 實驗結果
(一) 斑馬魚發育時期 NMDA 接受器之表現............................ 18
(二) 右美沙芬對胚胎孵化率及存活率之影響............................ 18
(三) 右美沙芬對稚魚外觀之影響...................................... 18
(四) 右美沙芬對骨頭發育之影響................................... 19
(五) 麩胺酸對胚胎孵化率及存活率之影響............................. 19
(六) 麩胺酸對稚魚外觀之影響..................................... 19
(七) 麩胺酸對骨頭發育之影響..................................... 20
(八) 先給予右美沙芬再給予麩胺酸對胚胎孵化率及存活率之影響......... 20
(九) 先給予右美沙芬再給予麩胺酸對胚胎外觀之影響................... 20
(十) 先給予右美沙芬再給予麩胺酸對骨頭發育之影響....................20
(十一) 右美沙芬及麩胺酸對熱休克蛋白Hsp25 蛋白質表現之影響......... 21
(十二) 右美沙芬及麩胺酸對熱休克蛋白Hsp90 蛋白質表現之影響......... 21
(十三) 右美沙芬及麩胺酸對phospho-ERK 蛋白質表現之影響............ 21

第四章 討論
(一) 右美沙芬對斑馬魚稚魚下顎異常與骨頭發育遲緩之影響..............49
(二) 麩氨酸系統對硬骨形成之影響.................................... 50
(三) 蝕骨細胞於骨頭發育時期扮演之角色............................. 51
(四) 熱休克蛋白之表現............................................. 51
(五) 細胞外信號調節酶ERK 蛋白質之作用............................. 52
(六) 藥物之吸收................................................... 53
(七) 未來展望..................................................... 53

第五章 附錄
附錄1、麩胺酸接受器之分類示意圖.................................... 55
附錄2、軟骨內骨化形成硬骨之過程.................................... 56

第六章 參考文獻
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