古柯鹼與安非他命調控轉錄因子胜肽 (Cocaine- and amphetamine- regulated transcript peptide, CARTp)廣泛的分布在中樞神經系統。被認為可做為神經調控者或者是神經傳訊者以參與許多神經生理反應；諸如藥物成癮、飲食調控、內分泌調控、焦慮等。前腹外側延腦 (rostral ventrolateral medulla, RVLM) 為中樞興奮交感神經之核區；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。解剖學上的證據指出位於RVLM的神經元及神經纖維含有大量CARTp。
這些結果暗示了CARTp可能參與RVLM的心血管功能調控。有研究指出投與CARTp到孤立束核(nucleus tractus solitaries, NTS) 雖無法使血壓上升卻可以減弱phenylephrine引起的心搏徐緩，而此作用可被CARTp之抗體阻斷。其他研究則指出將更高濃度的CARTp投與至中樞，即可造成血壓顯著上升。麩胺酸 (glutamate) 是這些中樞交感神經相關之神經核主要調控心血管功能的神經傳導物質；許多研究指出，磷酸化RVLM上離子型通道型麩胺酸受體－NMDA受體 (N-methy-D-asparate receptors, NMDARs) ，可增強該受體功能，進而增加中樞交感活性之輸出。我們的研究發現經由雙側RVLM投與CARTp (6, 30或60 pmol)可劑量依賴性升高血壓及降低感壓反射敏感度。此外，以側腦室處注射CARTp(20 pmol或2 nmol)， RVLM區NMDA受體次單位NR1上的磷酸化serine 897蛋白質表現量增加，而此磷酸化作用是經由A型蛋白激酶 (protein kinase A, PKA)路徑所作用。研究結果顯示CARTp可能藉由直接作用於RVLM引發升壓反應或藉由間接降低此區之感壓反射敏感度參與中樞之心血管調節，而PKA訊息路徑也許與此反應有關。

CARTp(Cocaine- and Amphetamine- regulated transcript peptide) is widely distributed in CNS as neurotransmitter or neuroregulator involved in many physiological process like addiction, food intake, endocrine and anxiety. The rostral ventrolateral medulla (RVLM) is critical to the tonic and reflexive regulation of arterial blood pressure. CARTp-immunoreactivity was detected in the neurons and nerve terminals in the RVLM. These evidence indicated CARTp may involve in RVLM regulated and increase blood pressure. Previous studies shows bilateral intra-NTS of CARTp (55-102, 0.1-3 nmol) could not change blood pressure but attenuated phenyleprine- induced bradycardia and reversed by CART-antibodies. The other studies shows higher dose CARTp injection into CNS could increase blood pressure. Results from many studies have revealed that phosphorylation of the ionotropic glutamate receptor- NMDA receptors (NMDARs) on the RVLM will increase the receptor function which leads to an increase in central sympathetic outflow. Our results found that bilateral microinjection of CARTp(6 30 60 pmol) into the RVLM decreased the baroreflex sensitivity (BRS) and increased the mean blood pressure. This study implied that CARTp may participate in the central cardiovascular regulation by direct pressor effects and indirect attenuation of the BRS. In addition, CARTp(20 pmol, 2 nmol) injection by intracerebroventricular (i.c.v.) induced a significant increase in the expression of the phosphoserine 897 protein (regulated by PKA) on NR1 subunit in the RVLM. Our results display CARTp may affect RVLM directly in pressor reponses, and indirectly affects in attenuated BRS to regulated central cardiovascular function. In addicition, the PKA signaling pathway may involved in these mediated functions.

中文摘要 1
英文摘要 2
壹、背景介紹 3
貳、研究目的與實驗設計 17
参、實驗方法材料與詳細步驟 21
肆、結果 25
伍、討論 29
陸、結論 33
柒、參考文獻 34
捌、結果附圖 44
附圖一 52
附錄一 53

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