跳到主要內容

臺灣博碩士論文加值系統

(44.200.27.215) 您好!臺灣時間:2024/04/20 08:59
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:李業寧
研究生(外文):Li, Yeh-Ning
論文名稱:比較三種由吳茱萸所抽取之生物鹼dehydroevodiamine,evodiamine及rutaecarpine在大白鼠心臟血管系統的作用
論文名稱(外文):Comparison of cardiovascular effects of dehydroevodiamine, evodiamine and rutaecarpine in rats
指導教授:沈友直陳介甫陳介甫引用關係
指導教授(外文):Shum, Yau-ChikChen, Chieh-Fu
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
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:1994
畢業學年度:82
語文別:中文
中文關鍵詞:藥物學藥學吳茱萸心臟血管
外文關鍵詞:PHARMACOLOGYDRUGS
相關次數:
  • 被引用被引用:0
  • 點閱點閱:197
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
Dehydroevodiamine(DeHE)、evodiamine(Evo)及rutaecarpine(Rut)為傳統中藥材-芸香科吳茱萸未成熟果實中所抽取之生物鹼,三者之化學構造非常類似,據過去之研究發現此三種生物鹼具有心臟血管方面的作用。本論文之目的即在利用活體動物及離體器官來研究並比較此三種生物鹼在大白鼠心臟血管系統作用。活體試驗為利用可植入動物體內之感應器,監測清醒且可自由活動動物的血壓及心跳等生理參數。植入感應器一週後才進行實驗。以腹腔注射(i.P)的方式將三種生物鹼投予到自發性高血壓大白鼠(SHR)及其對照之正常血壓Wistar-Kyoto rats(WKY)大白鼠中發現,DeHE(2.5-20mg/Kg)可使SHR大白鼠之血壓下降,心跳被抑制,但對WKY大白鼠沒有作用。Evo(2.5-2mg/kg)可使SHR大白鼠血壓下降,心跳上升,但對WkY大白鼠沒有作用。Rut(2.5-20mg/Kg)對SHR大白鼠沒有作用,卻可使WKY大白鼠血壓上升。在利用WKY大白鼠心耳標本所做實驗結果發現DeHE(10-8-10-5M)使跳動速率下降,但可使收縮力上升,Evo(10-8-10-5M)及Rut(10-8- 10-5M)使跳動速率及收縮力上升,且作用為劑量依賴性。第二次投予DeHE對DeHE之作用沒有影響,但第二次投予Evo及Rut對跳動速率及收縮力的 作用降低,暗示Evo及Rut的作用有去敏感性。在進一步研究此等藥物之心 臟作用機轉之實驗中,預處理以足以使acetylcholine(10-6M)失效之 atropine(10-6M),發現對DeHE之作用不影響。暗示DeHE非為直接活化 muscarininc接受器而達到心動徐緩的作用。預先給予ganylyl cyclase抑制劑 methylene blue(10-5M)或nitric oxide synthase抑制劑L-NG-nitro arginine(1mM) 可拮抗DeHE對跳動速率的抑制作用,顯示DeHE的機轉有涉及 nitric oxide系統。預先給予propranolol(10-5M)不影響Evo之作用但可降低Rut對跳動速率的增加作用,暗示Rut之作用與活化同型交感神經接受器有關。以可使tyuamine(10-4M)之作用消失之劑量之reserpine(2.5mg/kg i.p.)預處理,並不影響Rut之作用,顯示Rut之作用非經由刺激交感神經末稍釋出兒茶酚胺所致。由以上結果得知,此三種生物鹼雖有著極類似的化學構造,但在心臟血管的作用卻顯著不同。
The structurally similar quinazoime alkaloids Dehydroevodiamme (DeHE), Evodiamine (Evo) and Rutaecarpine (Rut) are bioactive ingredients isolated from a Chinese medicinal herb Evodia rutaecarpa Jussieu (Rutaceae). Among the phannacological actions attributed to these compounds are cardiovascular effects. The present study investigated and compared the effects of DeHE, Evo and Rut on the cardiovascular system in the rat by both in vivo and in vitro experiments. In vivo experiments were conducted in conscious and freely moving rats by continously recording blood pressure and heart rate by biotelemetry using transmitters implanted intraperitonealy at least 1 week before the experiments. Intraperitoneal (i.p) administration of DeHE (2.5-20 mg/kg) decreased both the mean arterial pressure and heart rate in the Spontaneously Hypertensive Rat (SHR) but had no significant effect in the normotensive control Wistar-Kyoto Rat (WKY). Evo (2.5-20 mg/kg i.p.) increased heart rate but decreased blood pressure in SHR and had no significant effect in WKY. Rut (2.5-20mg/kg) had no significant effect on neither blood pressure nor heart rate in SHR but increased blood pressure in WKY. In vitro experiments using isolated auricle preparations from WKY indicated that DeHE (108-1-5M) decreased the spontaneous beating rate (BR) but increased the contractile force (CF) while Evo (1O-810-5 M) and Rut (1O-810-5M) increased both the spontaneous beating rate and contractile force. These cardiac effects were concentration-dependent. While treatments for a second time had no effects on the cardiac actions of DeHE they elicited only weakened responses on both CF and BR by both Evo and Rut, suggesting the occurrence of desensitization in these compounds.
In efforts directed at further elucidating the mechanism of action underlying the cardiac effects of these compounds, atropine (10-6M) at a dose that effectively blocked the action of acetycholine (10-6M) did not affect the actions of DeHE, suggesting that muscarinic receptor activation was not the mechanism responsible for its bradycardiac effects. In the presence of a guanylyl cyclase inhibitor methylene blue (10-5M) or a nitric oxide synthase inhibitor L-NG-nitro-arginine (1O-3M) the inhibitory effect of DeHE on beating rate was attenuated, indicating that nitric oxide (NO) might be involved in the action of DeHE. Propranolol (10-5M) pretreatment had no effect on Evo's action, but reduced the action of Rut on beating rate, suggesting that β - adrenoceptor activation might be involved in the action of Rut. Reserpine (2.5 mg/Kg i.p) pretreatment at a dose that effectively abolished the action oftyramine (10-4 M) had no effect on the action of Rut, indicating that the action of Rut was not mediated through the release of catecholamines from sympathetic neuronal terminals. In summary, results from the present series study indicated that these three compoinds, although very similar in structure, possessed significant differences in cardiovascular properties.



QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊