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研究生:林佳慧
研究生(外文):Chia-Hui Lin
論文名稱:一氧化碳、腺苷及麩氨酸在大鼠孤立束核內心臟血管作用之研究
論文名稱(外文):Cardiovascular Effects of Carbon Monoxide, Adenosine and Glutamate in the Nucleus Tractus Solitarii of Rats
指導教授:曾清俊曾清俊引用關係
指導教授(外文):Ching-Jiunn Tseng
學位類別:碩士
校院名稱:國立中山大學
系所名稱:生物醫學科學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:85
中文關鍵詞:孤立束核一氧化碳腺苷麩氨酸
外文關鍵詞:glutamateadenosinenucleus tractus solitariicarbon monoxide
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  • 被引用被引用:1
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一氧化碳(carbon monoxide, CO)在腦中被認為是一內生性的生物訊息分子。原血紅素氧化酶(heme oxygenase, HO)分解原血紅質(heme)而產生一氧化碳與膽綠素。在腦中,一氧化碳為一神經傳導物質與神經元的訊息分子。我們過去曾發現一氧化碳參與了中樞心臟血管調控作用與感壓反射的作用,而且許多研究指出一氧化碳會影響麩氨酸的神經傳導作用,進一步的研究則發現活化 metabotropic 麩氨酸接受器(metabotropic glutamate receptors, mGluRs)與原血紅素氧化□之活化而產生的一氧化碳有關。另外,我們也曾經報導腺苷會促進孤立束核中麩氨酸的釋放。本研究主要的目的為探討一氧化碳在孤立束核中與腺□及 mGluRs 可能之相互作用與影響。實驗採用雄性 Sprague-Dawley 大鼠,以 urethane麻醉進行動脈插管來監測血壓與心跳之變化。單邊微量注射一氧化碳前趨物 hemin(0.01 - 3.3 nmol)到孤立束核會產生劑量相關性的血壓下降與心跳速率下降。同樣地,微量注射腺苷以及 mGluRs 三種的特異性作用劑 DHPG(group Ⅰ) (0.03 nmol)、APDC(group Ⅱ)(0.3 nmol)、L-AP4(group Ⅲ)(0.3 nmol)到孤立束核中,也會產生相似降血壓與心跳速率的作用。 Hemin 的這些心臟血管作用會被前處理腺苷接受體的拮抗劑 DPSPX(0.92 nmol)所減弱;相對的,分別前處理兩種原血紅素氧化□抑制劑 ZnPPⅨ 及 ZnDPBG(0.1 - 3.3 nmol)均會劑量相關性地減弱腺□的降血壓與心跳速率的作用。而前處理 ZnPPⅨ(0.1 - 1 nmol)會顯著的抑制 APDC 與 L-AP4 的降血壓與心跳速率的作用,而 DHPG 對心臟血管的作用則無顯著影響。這些結果顯示在中樞心臟血管的調控作用中一氧化碳與腺苷可能有著相互作用的情形,且推測 group Ⅱ 與 Ⅲ 的mGluRs 作用與原血紅素氧化酶之活化與進一步產生的一氧化碳有關。
Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase (HO) catalyzes the metabolism of heme to CO and biliverdin. CO has been shown to act as a neurotransmitter and neuronal messenger in the brain. We reported recently that CO was involved in central cardiovascular regulation, modulated the baroreflex, may affect glutamatergic neurotransmission, and metabotropic glutamate receptors (mGluRs) may be coupled to the activation of HO in the nucleus tractus solitarii (NTS) of rats. We also reported previously that adenosine can increase the release of glutamate in the NTS. The present study was designed to investigate the possible interaction of CO, adenosine, and mGluRs groups in the NTS. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of ascending doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by HO to yield CO, produced decreases in blood pressure and heart rate dose-dependently. In addition, similar cardiovascular effects were observed in adenosine (2.3 nmol) and several agonists for mGluRs groups such as DHPG (group Ⅰ) (0.03 nmol), APDC (group Ⅱ) (0.3 nmol)and L-AP4 (group Ⅲ) (0.3 nmol). These cardiovascular effects of hemin were attenuatd by prior administration of the adenosine receptor antagonist DPSPX (0.92 nmol). Similarly, pre-treatment of HO inhibitor ZnPPⅨ or ZnDPBG (1 nmol) also attenuated the depressor and bradycadic effects of adenosine. Among the mGluRs agonists, prior administration of ZnPPⅨ (1 nmol), an inhibitor of HO activity, significantly attenuated the cardiovascular effects of APDC and L-AP4, and failed to prevent the cardiovascular responses of DHPG. These results indicated an interaction between CO and adenosine, and group Ⅱ and Ⅲ mGluRs may be coupled to the activation of HO in central cardiovascular regulation.
序言....................1
材料與方法.................17
結果....................26
討論....................33
結論....................39
參考文獻..................40
表.....................51
圖.....................52
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