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研究生:朱俐穎
研究生(外文):Li-Ying Chu
論文名稱:古柯鹼及安非他命調控之轉錄胜肽於自發性高血壓大鼠前腹外側延腦區之心血管作用
論文名稱(外文):Cardiovascular Effect of Cocaine- and Amphetamine-Regulated Transcript Peptide in the Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats
指導教授:林恂恂林恂恂引用關係
指導教授(外文):Hsun-Hsun Lin
口試委員:袁宗凡李哲夫
口試委員(外文):Zung-Fan YuanJF Lee
口試日期:2014-06-30
學位類別:碩士
校院名稱:慈濟大學
系所名稱:生理暨解剖醫學碩士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:47
中文關鍵詞:古柯鹼及安非他命調控之轉錄胜肽自發性高血壓大鼠前腹外側延腦區
外文關鍵詞:Cocaine- and Amphetamine-Regulated Transcript PeptideSpontaneously Hypertensive RatsRostral Ventrolateral Medulla
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古柯鹼與安非他命調控轉錄因子胜肽(Cocaine- and amphetamine-regulated transcript peptide, CARTp)廣泛分布於大鼠的中樞神經系統,特別表達於自主神經和內分泌功能的控制區域。前腹外側延腦區(rostral ventrolateral medulla, RVLM)為中樞興奮交感神經之腦區,已知在持續性與反射性交感神經血壓調節作用中扮演重要角色,而研究亦發現此處之神經元及神經末梢皆有CARTp之免疫活性表現。於urethane麻醉的SD大鼠中樞給予CARTp,會引起血壓升高並同時伴隨RVLM區有顯著的c-Fos表現量增加現象。我們之前的研究顯示,在麻醉的SD大鼠雙邊給予三種不同劑量(6, 30, 60 pmol)的CARTp於RVLM腦區,會造成平均動脈壓(mean arterial pressure, MAP)的上升。這些證據皆暗示RVLM可能是CARTp參與中樞心血管調節的標的。在本實驗中發現,在雙側RVLM給予高劑量(30 pmol)的CARTp會造成自發性高血壓大鼠(spontaneously hypertensive rats, SHRs)和正常血壓大鼠(normotensive Wistar-Kyoto rats, WKY rats)的平均動脈壓升高;而給予低劑量(6 pmol)的CARTp只會造成SHR的血壓上升,WKY大鼠血壓不受影響。另外,雙側RVLM給予CARTp antibody (1:5000),會造成SHR平均動脈壓的下降,但是不影響WKY大鼠的血壓。為了證實藥物的作用,將CARTp(30 pmol)與CARTp antibody(1:5000)混合後注入雙側RVLM,可以發現SHR和WKY大鼠其血壓皆不受影響。採用免疫組織化學染色的方式,比較SHR及WKY兩種品系大鼠,將染到CARTp的神經元進行計數,從實驗可以得知,SHR大鼠其RVLM染到CARTp的神經元數量明顯多於WKY。我們的實驗結果表示, SHR大鼠的病理生理現象-自發性高血壓,其中CARTp參與其高血壓的維持。
Cocaine- and amphetamine-regulated transcript peptide (CARTp) is widely expressed in the rat central nervous system, notably in areas involved in control of autonomic and neuroendocrine functions. CARTp-immunoreactivity was detected in the neurons and nerve terminals of the rostral ventrolateral medulla (RVLM) which is critical to the tonic and reflexive regulation of arterial blood pressure. In urethane anesthetized Sprague-Dawley (SD) rats, central administration of CARTp can induce significant increases in blood pressure, which accompanied an increase of c-Fos-like immunoreactivity in the RVLM. Our previous studies showed that bilateral microinjection of CARTp (6, 30 or 60 pmol) into the RVLM increased the mean arterial pressure (MAP) in SD rats. These evidences implicated that the RVLM may be the central target structure for CARTp participating in the cardiovascular regulation. In this study, we found that bilateral microinjection of CARTp 30 pmol into the RVLM increased the MAP in both spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats, but significant pressor effect of low dose CARTp (6 pmol) was observed only in SHRs. Bilateral intra-RVLM injections of CARTp antibody (1:5000) decreased the MAP in SHRs but not WKY rats. Concomitant administration of CARTp (30 pmol) and CARTp antibody (1:5000) into the RVLM did not cause changes of MAP in both SHRs and WKY rats. Using immunohistochemistry study, the number of CARTp-immunoreactive neurons in the RVLM was counted in WKY rats and SHRs. SHRs presented a greater number of CARTp neurons in the RVLM than WKY rats. Our data suggest that CARTp is involved in the pathophysiology and maintenance of high blood pressure in the SHR.
中文摘要……………………………………………………………...…………….…..01
英文摘要……………………………………………………………...…….………..…02
壹、 背景介紹
A. 古柯鹼和安非他命調控之轉錄胜肽(CARTp)…………………………....…03
B. 前腹外側延腦與血管張力活性的維持與血壓調控………………….......…08
C. 自發性高血壓老鼠與正常血壓之老鼠其交感神經活性與血壓之關……...10
貳、 研究目的與實驗設計……………………………………………….………….....12
參、 實驗方法材料與詳細步驟…………………………………………..…..………..16
肆、 結果
一、 使用免疫組織化學染色,比較SHR和WKY兩種品系大鼠其RVLM
腦區之內生性CARTp的表現………………………………….……………22
二、 雙側RVLM以微量注射直接投與CARTp (6, 30 pmol),對血壓的影響…23
三、 雙側RVLM以微量注射直接投與CARTp antibody (1:5000),對血壓
的影響. ………………………………………...…………………………….24
四、 混合CARTp (30 pmol)與CARTp antibody (1:5000)以微量注射至雙側RVLM,對血壓的影響……………………………………………….......….25
伍、 討論
一、 SHR和WKY大鼠其RVLM內生性CARTp的表現量………….......……26
二、 RVLM給予CARTp(6,30 pmol) 之作用…………………………….....……27
三、 中樞給予CARTp antibody (1:5000)之作用…………………………………28
陸、 結論………………………………………………………………..…………..…..30
柒、 參考文獻………………………………………………………............…………..31
捌、 結果附圖………………………………..……………………………………..…..38
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