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研究生:賴怡璇
研究生(外文):Yi-Hsuan Lai
論文名稱:山刈葉根材水層萃取物在自發性高血壓大白鼠之抗高血壓作用
論文名稱(外文):The Antihypertensive Effects of Root Wood Extracts of Melicope Semecarpifolia in Spontaneously Hypertensive Rats
指導教授:施承典施承典引用關係
指導教授(外文):Cheng-Dean Shih
學位類別:碩士
校院名稱:大仁科技大學
系所名稱:製藥科技研究所
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:2006
畢業學年度:94
語文別:中文
論文頁數:79
中文關鍵詞:交感神經活性抗高血壓作用山刈葉一氧化氮自發性高血壓大白鼠
外文關鍵詞:SHRsympathetic toneantihypertensiveMelicope semecarpifolianitric oxide
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山刈葉 (Melicope semecarpifolia) 為芸香科雙子葉常綠植物,通常分佈在台灣和菲律賓中低海拔的森林裡,根材在民間療法中常被當作驅風劑。本篇主要探討山刈葉根材萃取物對自發性高血壓大白鼠之抗高血壓作用,單一靜脈注射不同劑量之水層萃取物(WSF, 10-100 mg/kg) 會產生雙向劑量依賴性抗血壓及降心跳作用,WSF之初期降血壓及心跳作用發生在5分鐘內,而後期反應發生於給藥後50分鐘並持續至120分鐘。在預給神經節阻斷劑hexamethonium bromide (單一靜脈注射:15或30 mg/kg;持續靜脈輸注:3 或6 mg/kg/min, 5分鐘),皆會明顯拮抗WSF (25 mg/kg) 產生的初期血壓及心跳下降作用。同樣在預給非選擇性的一氧化氮合成酶抑制劑NG-nitro-L-arginine methyl ester (單一靜脈注射:20 mg/kg;持續靜脈輸注:0.325 mg/kg/min, 5分鐘),選擇性內皮性一氧化氮合成酶抑制劑 5-(1-iminoethyl)-L-ornithine dihydrochoride (1 mg/kg/min) 或選擇性誘導性一氧化氮合成酶抑制劑S-methylisothiourea sulfate (0.5 mg/kg/min) 皆可以明顯拮抗WSF產生的後期血壓下降。再者,預給methylatropine bromide (1 mg/kg) 明顯減少WSF產生的心跳減緩,但卻不影響其抗高血壓作用。而預給propranolol hydrochloride (2 mg/kg) 則發現不會影響WSF產生的血壓和心跳下降之作用。

由結果得知,WSF產生的初期及後期抗高血壓作用分別和抑制交感神經活性,和活化內皮性一氧化氮合成酶以及誘導性一氧化氮合成酶所生成之一氧化氮有關。此外,WSF造成之心跳減緩作用可能經由直接活化心臟迷走神經而產生。
Melicope semecarpifolia (Rutaceae) is a dicotyledons evergreen tree distributed in lower altitude forest in Taiwan and the Philippines. The root wood of this plant has been used as a carminative in folk medicine. The present study aims to investigate the antihypertensive activity of the root wood extracts of Melicope semecarpifolia in spontaneously hypertensive rats (SHR). The intravenous bolus injection of the plant water-soluble fraction (WSF, 10-100 mg/kg) caused significant biphasic dose-related antihypertensive and bradycardiac responses. The WSF-induced initial hypotensive and bradycardiac effects lasted for 5 min and the delayed effects commenced 50 min and lasted for at least 120 min postinjection. The initial but not the delayed depressor effects of WSF (25 mg/kg, i.v.) were blocked by pretreatment of a ganglionic blocker, hexamethonium bromide (3 or 6 mg/kg/min for 5 min, or 15 or 30 mg/kg, i.v.). In contrast, pretreatment with nonselective nitric oxide (NO) synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (0.325 mg/kg/min for 5 min or 20 mg/kg, i.v.), selective endothelial NOS (eNOS) inhibitor, 5-(1-Iminoethyl)-L-ornithine dihydrochloride (1 mg/kg/min for 5 min) or selective inducible NOS (iNOS) inhibitor, S-methylisothiourea sulfate
(0.5 mg/kg/min for 5 min) significantly reversed the delayed but not the initial depressor effects of WSF. Furthermore, pretreatment with methylatropine bromide (1 mg/kg, i.v.) significantly reduced the bradycardia without affecting antihypertensive effects of WSF, but pretreatment with propranolol hydrochloride (2 mg/kg, i.v.) did not affect this both effects.
These results indicate that WSF from root wood of Melicope semecarpifolia elicited both transient and delayed antihypertensive actions that is mediated by a withdrawal of sympathetic tone, and NO generated by eNOS and iNOS. The bradycardiac activity of WSF may result from a direct vagal activation upon the heart.
目 錄
頁數
中文摘要…….………………………………………………………………...I
Abstract…………………………….…………….………………………III
縮寫表…………………………………………………………………...…...V
圖表目錄……………………………………………………………...……VII

第一章、緒論與文獻回顧……………………..………….……………..…..1
第一節 山刈葉之介紹..………………..……….……………..…..1 第二節 山刈葉根材萃取化合物相關活性介紹...………………..2
第三節 調控血壓的機制………………..…….………..……..…..4
第四節 動脈壓的頻譜分析……………..…………………….…..6
第五節 一氧化氮………………………..……….……..……..…..7
第六節 高血壓的介紹…………………..……….…..………..…..9
第七節 高血壓的治療…………………..………………….....…11
第二章、研究動機與目的…………………….……………….………...…16
第一節 研究動機………….……………..………….………...…16
第二節 研究目的………………......…….……….…………...…16
第三章、實驗方法與材料.…………………….……………….………..…18
第一節 實驗材料與儀器….……………..………….………...…18
第二節 基本手術處理…………......…….……….…………...…19
第三節 實驗步驟………………......…….……….…………...…21
第四章、實驗結果………….…………….…….……………….………...…25
第五章、討論……………….…………….…….……………….………...…31
第六章、結論……………………………..…….……………….………...…38
第七章、未來展望………….………………….……………….………...…39
參考文獻…………...……….………………….……………….…………...41
圖表....…………………………………………………………………….....50
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