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系統識別號 U0007-0108201114050300
論文名稱(中文) 葛根素促進骨母細胞代謝的作用機轉
論文名稱(英文) The Action Mechanism of Puerarin on Osteoblast Metabolic Promotion
校院名稱 臺北醫學大學
系所名稱(中) 藥學研究所
系所名稱(英) Graduate Institute of Pharmacy
學年度 99
學期 2
出版年 100
研究生(中文) 蔡佳純
研究生(英文) Chia-Chung Tsai
學號 M301098037
學位類別 碩士
語文別 中文
口試日期 2011-06-30
論文頁數 87頁
口試委員 指導教授-許秀蘊
共同指導教授-孫瑞昇
委員-蔡東湖
委員-蔡麗雪
中文關鍵字 骨質疏鬆症  葛根素  骨母細胞 
英文關鍵字 Osteoporosis  puerarin  osteoblast 
學科別分類
中文摘要 逐漸踏入高齡化社會,停經後女性因為體內雌激素減少,容易發生骨質流失,造成骨質疏鬆的機率相對提高,也增加骨折的風險,導致生活上的不便。治療骨質疏鬆的治療方針為賀爾蒙替代療法(hormonal replacement therapy;HRT),會有冠狀心臟疾病及中風的風險存在。近年來發現植物萃取物中含有類似雌激素的植物雌激素,作用和雌激素相仿,像是大豆中的genistein、daizein,因為結構中有異黃酮(isoflavone)骨架,所以稱之為植物雌激素(phytoestrogen)。葛根素(Puerarin)也有異黃酮骨架,本研究探討葛根素是否可以取代雌激素成為治療骨質疏鬆症的較安全藥物。
本研究以八個月大的母鼠(ICR)為動物模式,這樣動物模式的骨質程度和停經後女性的骨質情況相當,探討給予葛根素對於骨母細胞的影響,分別在第3,7,14天利用細胞活性、鹼性磷酸酶、礦化、西方點墨法及即時定量反轉錄聚合酶連鎖反應來討論葛根素對骨母細胞的影響。
結果發現,以年老的母鼠骨母細胞實驗模式下,葛根素可以增加細胞的存活,在10-8M有最高的促進率。所以葛根素對於細胞有增生作用,但在新生鼠骨母細胞沒有促進細胞活性,所以本實驗以八個月大的母鼠為動物模式,葛根素對於年老母鼠有良好的反應。
實驗結果發現10-8 M Puerarin會刺激骨母細胞增生,增加分泌ALP、骨礦化作用及釋放NO的能力較好。Puerarin會增加BMP-2、SMAD4及Cbfa1/Runx2mRNA表現。利用Noggin 與L-NAME來探討相關的機轉,發現其可以抑制ALP、NO及細胞活性。所以Puerarin刺激成骨母細胞增生及分化,經由Estrogen receptorβ去影響了NO及BMP-2生成及途徑。Puerarin對於骨母細胞造成成骨作用,是透過BMP-2/Smad及NO途徑。NO會活化MAPK相關的JNK、ERK和p38,導致骨母細胞增生及分化。BMP-2/Smad也會活化MAPK造成骨母細胞成骨的作用。因此,推測葛根素可能對於停經後女性的骨質疏鬆有正面的影響。
英文摘要 Osteoporosis poses a major threat to individual and public health due to the high morbidity and mortality associated with fragile fractures. Estrogen deficiency, which occurs in post-menopausal women, which results in higher levels of bone resorption than bone formation, hence a net loss in bone mass. Medical treatment of osteoporosis include of bisphosphonate, selective estrogen receptor modulators (SERMs), calcitonin, vitamin D analogues, parathyroid hormone (PTH) and hormonal replacement therapy ( HRT). Those treatments had various disadvantages.
Phytoestrogens are plant-derived non-steroidal compounds with estrogen-like activity that bind to estrogen receptors. Phytoestrogens are divided into three classes: isoflavone, coumestans and lignans. Puerarin is isolated from the root of a wild leguminous creeper, Pueraria lobata (Willd.) Ohwi. The structure contains isoflavone. It is possible that puerarin may also increase the bone formation. The main aim of this study was to investigate the mechanism of puerarin on osteoblast metabolism.
In this study, we assessed the effects of the phytoestrogen on cell proliferation, alkaline phosphatase activity and mineralization in osteoblast from 8-months old female Imprinting Control Region (ICR) mice. The cells transcriptionally expressed the detectable levels of BMP-2, SMAD4, Cbfa1/Runx2, OPG and RANKL mRNAs.
論文目次 中文摘要 VI
英文摘要 VIII
縮寫對應 IX
表目錄 XIII
緒論 1
1-1前言 1
1-2研究背景 4
1-3研究目的 5
第二章理論基礎 6
2-1骨骼組織Histology of bones 6
2-1-1骨骼組織Histology of bones 6
2-1-2骨細胞Bone cell 7
2-1-3骨母細胞Osteoblast 7
2-1-4骨細胞Osteocyte 9
2-1-5蝕骨細胞Osteoclast 9
2-2-1骨母細胞的生理 11
2-2-2骨形態發生蛋白Bone morphogenetic proteins (BMPs) 12
2-2-3 NO對骨母細胞的影響 15
2-3葛根 16
2-4-1骨質疏鬆症 18
2-4-1-1原發性骨質疏鬆 18
2-4-1-2次發性骨質疏鬆 19
2-4-2骨質疏鬆症危險因子 20
2-4-3骨質疏鬆症的影響 20
2-4-4骨質疏鬆症的診斷 21
2-4-5骨質疏鬆的治療 23
2-4-6骨質疏鬆症的預防 25
2-5雌激素與植物雌激素 26
2-5-1雌激素 26
2-5-2雌激素對於骨母細胞分化的影響 27
第三章 材料與方法 28
3-1材料 28
3-1-1實驗儀器 28
3-1-2實驗試藥與材料 29
3-2方法 31
3-2-1試藥配製 31
3-2-1-1細胞培養試藥 31
3-2-1-2 Puerarin藥品配製 32
3-2-1-3 Cycloheximide試藥配製 33
3-2-1-4 Noggin試藥配製 34
3-2-1-5 Nω-nitro-L-arginine methyl ester (L-NAME) 試藥配置 34
3-2-1-6細胞活性分析試藥配製 34
3-2-1-7細胞一氧化氮分析試藥配製 35
3-2-1-8細胞礦化Alizarin Red-S 染色試藥配製 35
3-2-1-9西方點墨法試藥配製 36
3-2-2骨母細胞培養 38
3-2-3細胞活性分析 40
3-2-3-1 MTT分析原理 40
3-2-3-2 細胞活性方法 41
3-2-4 鹼性磷酸酶活性分析 41
3-2-4-1鹼性磷酸酶活性分析原理 41
3-2-4-2鹼性磷酸酶活性分析步驟 41
3-2-5 細胞礦化分析 42
3-2-5-1細胞礦化分析原理 42
3-2-5-2 細胞礦化實驗步驟 42
3-2-6 細胞一氧化氮分析 43
3-2-6-1 細胞一氧化氮分析原理 43
3-2-6-2 細胞一氧化氮分析步驟 43
3-2-7 西方點墨法 44
3-2-8 即時定量反轉錄聚合酶連鎖反應 46
3-2-8-1抽取RNA步驟 46
3-2-8-2 Total RNA 含量分析 47
3-2-8-3反轉錄 (reverse transcriptase, RT) 合成cDNA 47
3-2-8-4即時定量聚合酶連鎖反應使用之引子Primer 49
3-2-8-5即時定量聚合酶連鎖反應 (Real-Time qPCR) 50
第四章 結果 51
4-1細胞活性分析 51
4-2鹼性磷酸酶分析 54
4-3細胞礦化分析 56
4-4細胞一氧化氮分析 57
4-5蛋白質抑制劑分析 57
4-6即時定量聚合酶連鎖反應 57
4-7 L-NAME和Noggin抑制劑分析 57
4-8西方點墨法 57
第五章 討論 57
第六章 總結 57
參考文獻 57

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