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研究生:王丞汝
研究生(外文):WANG,CHENG-JU
論文名稱:Fg Bβ15-42胜肽之抗高血壓活性研究
論文名稱(外文):The Study of Antihypertensive Activity of Fg Bβ15-42 Peptide
指導教授:施承典施承典引用關係
指導教授(外文):SHI,CHENG-DIAN
口試委員:謝登恩連文彬
口試委員(外文):SHIEH,DEN-ENLIAN,WEN-BIN
口試日期:2020-06-04
學位類別:碩士
校院名稱:大仁科技大學
系所名稱:藥學系碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:66
中文關鍵詞:Fg Bβ15-42 胜肽高血壓一氧化氮心血管活性
外文關鍵詞:Fg Bβ15-42 peptideHypertensionNitric oxideCardiovascular activities.
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目前我國十大死因中,因心臟血管疾病死亡率較高,如高血壓等所造成的死亡一直名列前茅,因此治療與預防藥物的開發,一直是醫藥界研究探討的熱門話題。近年研究發現由動植物天然食材中一些胜肽類物質具有抑制血管張力素轉換酶(Angiotensin-converting enzyme, ACE)的活性而減少血管張力素II (Angiotensin II)的形成,因而達到調節血壓的效果。因此,開發具有調節血壓功效之保健食品或植物性產品來預防或改善高血壓,將是多數病患所樂於接受。
過去研究發現,Fg Bβ15-42胜肽(28個胺基酸)是一種纖維蛋白原(Fibrinogen, Fg)經過酵素分解的天然產物,該內生性胜肽在離體實驗中證實,具有增加血管內皮細胞一氧化氮(Nitric oxide, NO)的生體可用率(Bioavailability),顯示該胜肽在誘發一氧化氮產生中扮演重要的調控角色。
再者,高血壓的病理機轉也和血管內皮細胞一氧化氮產生異常有關,本研究發現該胜肽對於高血壓狀態之活體動物具有顯著延遲且持久抗高血壓作用,並對心跳速率、心臟收縮力及血管運動活性亦有相同抑制效應,其機轉可能與阻斷交感神經性血管運動張力及調節血管內皮性一氧化氮形成有關,這也提供了高血壓治療應用上一個新的證據。
在實務應用上,將可開發具有調節心血管活性之保健食品或產品來預防或改善高血壓,更具發展成抗高血壓藥物之可能。

Among the top 10 causes of death in Taiwan, deaths due to cardiovascular diseases such as hypertension have been ranked among the top. Therefore, the development of therapeutic and preventive drugs has always been a hot topic in the medical field. According to recent research, some peptides in natural materials of plants and animals have the activity of inhibiting angiotensin-converting enzyme and reduce the formation of angiotensin II, thus regulating blood pressure effect. Therefore, the development of health foods or plant products with blood pressure regulation to prevent or improve hypertension will be accepted by most patients.
In vitro experiments, the previous study discovered that Fg Bβ15-42 peptide (28 amino acids) is a natural product of fibrinogen (Fg) decomposed by enzymes, endogenous peptides have been shown increased the bioavailability of nitric oxide (NO) in vascular endothelial cells indicates that this peptide plays an important regulatory role in the induction of NO production.
Furthermore, the pathological mechanism of hypertension is also associated with abnormal production of NO in vascular endothelial cells. The study found that the peptide has a significant delay and long-lasting antihypertensive effect on the living animals in the hypertensive state, and the heart rate, cardiac contractility and vasomotor activity also have the same inhibitory effect, and its mechanisms may were mediated by the withdrawal of the sympathetic neurogenic vasomotor tone and regulating the formation of vascular endothelial NO, which also provides a new evidence for the therapeutic application of hypertension.


中文摘要…………………………………………………………………....Ⅰ
英文摘要……………………………………………………………….....Ⅱ
誌謝…………………………………………………………….……………Ⅳ
目錄……………………………….………………………………….........Ⅴ
圖次目錄………………………………………………………………........Ⅶ
表次目錄……………………………………………………………..……Ⅷ
第一章 緒論………………………………………………………...………1
第一節 Fg Bβ15-42胜肽由來與介紹..........................................…...............1
第二節 Fg Bβ15-42胜肽心血管活性....………………...……………..……4
第三節 一氧化氮......……….........……………………...……………..….6
第四節 心血管調控....................………………………...……………..…9
第五節 Fg Bβ15-42胜肽與一氧化氮之關係…………………...………....12
第六節 高血壓...........................................................................................15
第七節 高血壓治療.............................................................................…..18
第八節 動脈壓訊號功率頻譜分析...........................................................21
第二章 研究動機與研究目的.....................................................................23
第一節 研究動機.......................................................................................22
第二節 研究目的.......................................................................................24
第三章 實驗材料與方法.............................................................................25
第一節 實驗器材…………………………..……………….……………25
第二節 基本手術原理………………………..…………............……….27
第三節 實驗步驟………………........……..……………............……….31
第四節 資料分析.......................................................................................33
第四章 研究結果............……………………………………...............….34
第五章 討論............………………………………………………….……45
第六章 結論............………………………………………………….……51
第一節 研究限制與建議………………..………………............……….51
第二節 未來展望………………………..………………….……………52
參考文獻………………………………….…………………………………53









圖次目錄
圖一 纖維蛋白原結構組成.............................................................................1
圖二 纖維蛋白原裂解流程.............................................................................2
圖三 人體Fg Bβ15-42胜肽序列.........................................................................3
圖四 一氧化氮合成.......................................................................……..........6
圖五 心血管調控...........................................................................................11
圖六 Rho調節機轉.......................................................................................13
圖七 Fg Bβ15-42胜肽細胞內之反應..............................................................14
圖八 Fg Bβ15-42胜肽與NO之關係..............................................................14
圖九 基本手術處理......................................................................................27
圖十 實驗操作示意圖..................................................................................28
圖十一 心臟導管及心臟收縮力評估示意圖..............................................29
圖十二 動脈壓訊號功率頻譜分析..............................................................30
圖十三 Fg Bβ15-42胜肽對平均動脈壓之影響.............................................35
圖十四 Fg Bβ15-42胜肽對心跳之影響.........................................................37
圖十五 Fg Bβ15-42胜肽對心臟收縮力之影響.............................................39
圖十六 Fg Bβ15-42胜肽對血管運動活性之影響.........................................41
圖十七 抑制劑對Fg Bβ15-42胜肽引發平均動脈壓與心跳抑制作用
之影饗..................................................................................................43
圖十八 抑制劑對Fg Bβ15-42胜肽引發心臟收縮力與血管運動活性抑制作用之影響.................................................................................................44

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