研究生: |
洪鈺婷 Hong, Yu-Ting |
---|---|
論文名稱: |
腦部SFO-PVN-RVLM路徑的血管收縮素接受器亞型在缺血性中風後升壓反應之角色 Role of brain angiotensin receptor isoforms at the SFO-PVN-RVLM pathway in pressor response after ischemic stroke |
指導教授: |
張雅雯
Chang, Alice Y.W. |
學位類別: |
碩士 Master |
系所名稱: |
醫學院 - 生理學研究所 Department of Physiology |
論文出版年: | 2017 |
畢業學年度: | 105 |
語文別: | 中文 |
論文頁數: | 116 |
中文關鍵詞: | 缺血性中風 、腎素-血管收縮素系統 、升壓反應 、穹窿下器官-視旁核-延腦鼻端腹外側核路徑 |
外文關鍵詞: | ischemic stroke, renin angiotensin system, pressor response, SFO-PVN-RVLM pathway |
相關次數: | 點閱:79 下載:0 |
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缺血性中風在全球十大死因當中為第二名,在西元2015年中大約有六百萬人死於中風,且在缺血性中風後約有60% 病患會伴隨著血壓增加現象。我們實驗室先前研究結果顯示延腦鼻端腹外側核的腎素-血管收縮素系統有參與在缺血性中風後血壓短暫增加的調控;此外,血管收縮素可作為神經傳遞物質,透過穹窿下器官-視旁核-延腦鼻端腹外側核路徑傳遞。文獻上也發現腎素-血管收縮素系統能夠調節血壓,但在缺血性中風後腦中穹窿下器官-視旁核-延腦鼻端腹外側核路徑之腎素-血管收縮素系統調控血壓機制尚未明瞭。因此,本實驗欲探討缺血性中風後血壓短暫增加是否藉由穹窿下器官-視旁核-延腦鼻端腹外側核路徑中的血管收縮素調控。首先,確認小鼠在缺血性中風後會伴隨短暫血壓增加,接著,分析血管收縮素受器基因與蛋白質和合成酵素基因,發現在視旁核的血管收縮素合成酵素在缺血性中風後會增加,但是穹隆下器官之合成酵素並不會,代表視旁核能製造血管收縮素並可在延腦鼻端腹外側核釋放。由於視旁核腎素-血管收縮素系統受器表現量並無增加,且穹隆下器官的血管收縮素之合成酵素也無增加,代表視旁核腎素-血管收縮素系統並非由穹隆下器官製造的血管收縮素活化。因此,接續發現視旁核的Toll-like receptors與mineralocorticoid receptor基因表現量增加,(Pro)renin receptor則沒有,認為視旁核的發炎反應能夠活化血管收縮素神經細胞。接著,將小鼠處理美諾四環素並誘導中風後發現抑制合成血管收縮素神經的活化;此外,能夠調控血壓的內源性大麻素在穹窿下器官-視旁核-延腦鼻端腹外側核路徑中也會受到美諾四環素抑制。總結以上,缺血性中風後的血壓增加反應是由於視旁核的發炎反應引起血管收縮素合成,但抑制發炎反應卻使得腎素-血管收縮素與內源性大麻素系統在穹窿下器官-視旁核-延腦鼻端腹外側核路徑中皆被抑制。
SUMMARY
About 60% of ischemic stroke patients were accompanied with transient pressor response within 24 h after ischemic stroke. Angiotensin II (Ang II) acted as a neurotransmitter through subfornical organ (SFO)-paraventricular nucleus (PVN)-rostral ventrolateral medulla (RVLM) pathway to regulate blood pressure (BP). This study aimed to explore brain mechanism which could regulate blood pressure after ischemic stroke. C57BL/6 mice were operated thromboembolic middle cerebral artery occlusion (eMCAO) surgery, which could mimic clinical situation. Also, mice were measured BP by non-invasive tail-cuff system. The results showed that brain inflammation induced by ischemic stroke could activate PVN neurons to increase Ang II synthesis enzymes, and increased BP transiently.
Key words: ischemic stroke, renin angiotensin system, pressor response, SFO-PVN-RVLM pathway
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