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研究生:陳信維
研究生(外文):Hsin-Wei Chen
論文名稱:牛蒡子對海綿體舒張之研究
論文名稱(外文):Study of Fructus Arctii on Corpus Cavernosum Relaxation
指導教授:郭代磺
指導教授(外文):Daih-Huang Kuo
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:2009
畢業學年度:97
語文別:中文
論文頁數:133
中文關鍵詞:舒張作用勃起障礙海綿體平滑肌威而鋼犀利士牛蒡子樂威壯
外文關鍵詞:Erectile DysfunctionFructus Arctii or Friuts Arctium lappa L.corpus cavernosum smooth muscleRelaxationVardenafilTadalafilSildenafil
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近年來男性的老化研究顯示,52%的受訪者具有一定程度的勃起功能障礙,35%的40-70歲的男性被認定為中度或完全的陽痿。男性無法產生或維持足夠硬度的陰莖勃起,達到滿意的性行為稱為勃起障礙。
在坊間有許多具有補陽功效的中藥,如:杜仲(Eucommia ulmoides Oliv.)、淫羊藿(Epimedium brevicornum Maxim.)、牛蒡(Arctium lappa L.)等。這之中的淫羊藿曾有學者做過進一步的研究發現,淫羊藿的粗萃物及分層萃取物在濃度為1mg/ml時,對兔離體海綿體平滑肌(Corpus cavernosal smooth muscle, CCSM)的舒張效應,各別為39%及34%;簡單的說,淫羊藿是具有幫助勃起的功效。
目前用於治療勃起功能障礙的西藥以PDE5 inhibitors為首選藥物,但這類藥物的副作用多以心血管為主,且有致死案例出現過。本研究目的在於找出具有改善勃起功能障礙且安全性比PDE5 inhibitors高的中草藥。首先以不同溶媒製備牛蒡子(Fructus Arctii or Friuts Arctium lappa L., FAL)四種粗萃物:FAL extract-A、B、C與D。我們發現FAL extrat-C、D在濃度為100μg/ml時,對雄兔離體CCSM的最大舒張活性90.56%( p < 0.001)、98.93% ( p < 0.001)。之後以FAL extract-D做分層萃取,得五個分層萃取物:HxF、DcF、EaF、BtF及WtF等,於CCSM舒張作用的評估實驗中,發現DcF、EaF與BtF等三層,在濃度為100μg/ml時,對雄兔的離體CCSM舒張活性為100%( p < 0.001)、100%( p < 0.001)與96.88%( p < 0.001)。另外從機轉實驗中發現FAL是經由抑制CCSM的α1 adrenergic receptor,而達到舒張CCSM的作用。
總結來說,FAL明顯抑制了CCSM的收縮作用,並且FAL是經由抑制α1 adrenergic receptor的作用,而促使 CCSM產生了舒張效應。所以我們認為FAL或許具有改善勃起障礙的的效用。
According some papers showed that 52% of respondents with some degree of erectile dysfunction and 35% of 40–70 years old men with moderate or complete impotence recently. Erectile dysfunction, known clinically as disorder about erection, is a medical problem affecting young and old men.
There are many traditional Chinese medicines in the market have the increase physical energy effect, include Eucommia ulmoides Oliv., Epimedium brevicornum Maxim., Arctium lappa L. fruits etc. The Epimedium brevicornum Maxim was investigated by some scholars in some studies. Epimedium brevicornum Maxim. crude extract and fraction extract possessed the 39% and 34% individually relaxation effect on rabbit corpus cavernosum smooth muscle (CCSM) at 1mg/ml. This effect indicated that Epimedium brevicornum Maxim was helpful to erection effect.
At present, PDE5 inhibitors were used for the treatment of erectile dysfunction but many side-effects in cardiovascular disorders and fatal cases have ever occurred. The aim of this study is to find folk medicine to improve erectile dysfunction and more safe than PDE5 inhibitor. First, Fructus Arctii or fruits Arctium lappa L. (FAL) were prepared by different solvents and metho, we could obtain crude extracted included: FAL extract-A、B、C & D. We found that FAL extracts-C and D (at 100μg/ml) were 90.58 % ( p<0.001) and 100% ( p<0.001) relaxation individually on CCSM. Then FAL extract-D was used to fraction partition by different solvents and five fractional extracts were obtained, included HxF、DcF、EaF、BtF & WtF. Three fractional extracts: DcF、EaF and BtF(at 100μg/ml) were 100%( p< 0.001)、100%( p< 0.001) and 96.88%( p< 0.001) on CCSM for the maximal relaxation effect. Additionally, the relaxation effect of FAL was mediated byα1 adrenergic receptor to inhibit the CCSM contraction.
In conclusion, the contraction of CCSM was actually inhibited by FAL and the relaxation effect was through inhibition of the α1 adrenergic receptor. So we suggested that FAL might be helpful to improve erectile dysfunction.
目錄
誌謝 I
中文摘要 II
Abstract III
目錄 V
表錄 VIII
圖錄 IX
第壹章 文獻回顧 11
第一節 認識勃起功能障礙 11
第二節 男性陰莖的構造解剖 12
第三節 男性勃起反應的生理機轉 15
第四節 生理學上的陰莖平滑肌收縮舒張的張力調節 17
(一)陰莖平滑肌的收縮 20
(二)在平滑肌細胞內收縮作用的調節機轉 22
第五節 勃起功能障礙原因 25
(一)器質性: 25
(二)心因性: 26
(三)混合性: 26
(四)藥物引起的勃起功能障礙: 26
(五)慢性疾病併發引起的勃起功能障礙: 27
第六節 勃起功能障礙的診斷與評估 27
(一)問診 27
(二)身體檢查 28
(三)血液檢查 29
(四)血管檢查 30
(五)陰莖夜間腫脹及硬度檢查 30
(六)勃起功能障礙的評估 31
第七節 勃起功能障礙的治療 32
(一)用於治療勃起功能障礙的西藥 32
(二)用於治療勃起功能障礙的中藥 40
(三)現代食療與補陽養身的相關性 53
(四)民間流傳與壯陽有關訊息 55
第八節 牛蒡的簡介 56
(一)牛蒡成分分析 57
(二)牛蒡之現代研究文獻整理 58
第九節 牛蒡子的簡介 61
(一)成分分析 61
(二)藥理作用 62
(三)性味、功效 62
(四)中醫臨床上的使用經驗 62
(五)牛蒡子之現代研究文獻整理 64
第十節 研究動機 65
第貳章 牛蒡子粗萃取及分配萃取 66
第一節 實驗材料 66
(一)牛蒡子 66
(二)試藥 66
(三)儀器及器材 66
第二節 實驗方法 67
(一)牛蒡子粗萃方法 67
(二)以牛蒡子粗萃物(FAL extract-D)做分層萃取方法 67
第三節 結果 68
(一)牛蒡子粗萃取 68
(二)以牛蒡子粗萃物(FAL extract-D)做分層萃取 68
第四節 討論 68
第參章 牛蒡子粗萃物及分層萃取物在離體活性的篩選 70
第一節 實驗材料 70
(一)實驗動物 70
(二)試藥 70
(三)儀器及器材 70
第二節 實驗方法 71
(一)Kreb solution的製備 71
(二)兔離體海綿體平滑肌的製備 71
(三)牛蒡子粗萃物活性篩選 75
(四)FAL複方粗萃物(FSD extract)及製劑(FSD product)活性篩選 75
(五)牛蒡子指標成分活性篩選 76
(六)牛蒡子分層粗萃物活性的篩選 76
第三節 結果 77
(一)牛蒡子各種粗萃物活性篩選 77
(二)FAL複方粗萃物(FSD extract)及製劑(FSD product)活性篩選 82
(三)牛蒡子指標成分活性篩選 83
(四)牛蒡子分層萃取物活性的篩選 84
第四節 討論 89
第肆章 牛蒡子萃取物之作用機轉探討 92
第一節 實驗材料 92
(一)實驗動物 92
(二)試藥 92
(三)儀器及器材 93
第二節 實驗方法 93
(一)Kreb solution的製備 93
(二)兔離體海綿體平滑肌的製備 93
(三)PDE5 inhibitors市售品活性確認 93
(四)牛蒡子萃取物作用機轉測試 93
第三節 結果 96
(一) PDE5 inhibitors市售品活性確認 96
(二)牛蒡子萃取物作用機轉測試 98
第四節 討論 112
第伍章 結論 114
第陸章 參考文獻 117
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