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研究生:陳燕玲
研究生(外文):Yen-Ling Chen
論文名稱:厚朴酚對於尿壓素誘發心臟纖維細胞增生的作用
論文名稱(外文):Effect of magnolol on urotensin II-induced cardiac fibroblast proliferation
指導教授:洪傳岳洪傳岳引用關係
指導教授(外文):Chuang-Ye Hong
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:91
中文關鍵詞:厚朴酚尿壓素活性氧族群胞外訊息調節激酶內皮素心臟纖維細胞增生
外文關鍵詞:magnololurotensin IIendothelin-1cardiac fibroblast proliferationreactive oxygen speciesextracellular signal-regulated kinase
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厚朴酚(Magnolol)是從中國草本植物厚朴所萃取出來的一種物質,具有抗氧化、抗血栓形成、抗焦慮、抗發炎、血管放鬆等藥理特性。近期的研究也發現會造成許多不同癌細胞株凋亡的作用。在心血管方面,厚朴酚會有抑制血管平滑肌細胞增生的作用,然而對於心臟纖維細胞的作用及相關的細胞分子機制都還不是很清楚。尿壓素(Urotensin-Ⅱ; U-Ⅱ)為目前已知具有強力促進血管收縮作用的內生性物質,而且與高血壓及心血管疾病如冠狀動脈硬化及心臟衰竭有密切關聯,動物實驗的結果顯示尿壓素對於心臟重塑及纖維化過程的發生會有促進的作用 (Lapp et al.,2004)。本研究目的即在於以培養的離體心臟纖維細胞,觀察尿壓素對於心臟纖維細胞的作用,並進一步探討厚朴酚是否會抑制由尿壓素所誘發心臟纖維細胞的作用,據以了解厚朴酚在尿壓素所誘發心臟纖維細胞作用的相關細胞分子機轉。
於培養的初生鼠心臟纖維細胞給予不同濃度尿壓素的處理後,發現尿壓素會促進心臟纖維細胞的增生,以及增加內皮素蛋白質的表現。至於細胞內的作用機制,尿壓素對細胞內活性氧族群以及胞外訊息調節激酶活性皆會有增加的作用。進一步觀察厚朴酚對於心臟纖維細胞的作用,單獨厚朴酚的處理,在30µM濃度以上,會造成細胞的毒性作用。厚朴酚在10µM濃度內,對於尿壓素增加細胞內活性氧族群、胞外訊息調節激酶活性、內皮素蛋白質表現以及細胞增生則會有抑制作用。
本研究結果發現尿壓素具有增加心臟纖維細胞內活性氧族群的產生、胞外訊息調節激酶活性、內皮素蛋白質表現,以及促進細胞增生的作用。尿壓素誘發心臟纖維細胞增生以及相關細胞內的作用則會被厚朴酚抑制,結果顯示厚朴酚或許將有助於尿壓素所誘發相關心臟纖維化之治療運用。
Magnolol, a compound extracted from the Chinese medicinal herb Magnolia officinalis, has several biological effects. Studies using purified magnolol have shown that it can function to scavenge hydroxyl radicals, inhibit neutrophil adhesion, suppress the inflammatory response and inhibit platelet aggregation. Of particular interest for the present study is the magnolol-induced apoptosis in a variety of cancer cells. It has been demonstrated that magnolol exerted potent inhibitory effects on the growth of vascular smooth muscle cells. However, the effects and mechanistic insights of mangolol on the cellular levels are not elucidated in cardiac fibroblasts.
As the most potent vasoconstrictor in mammals, urotensin II (U-II) has recently been demonstrated to play an important role in adverse cardiac remodeling and fibrosis. However, the mechanisms of U-II-induced myocardial fibrosis remain to be clarified. Therefore, the aims of this study were to determine the effect of U-II on cell proliferation and examine whether magnolol may alter U-II-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. Cultured rat cardiac fibroblasts were preincubated with magnolol then stimulated with U-II, BrdU incorporation and ET-1 secretion was examined. The effect of magnolol on U-II-induced reactive oxygen species (ROS) formation, and extracellular signal-regulated kinase (ERK) phosphorylation were tested to elucidate the intracellular mechanism of magnolol in proliferation and ET-1 secretion. U-II increased DNA synthesis which was inhibited with magnolol. Magnolol also inhibited U-II-increased ROS formation and ERK phosphorylation In summary, our results suggest that magnolol inhibits U-II-induced cell proliferation and ET-1 secretion, partially by interfering with the ERK pathway via attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of magnolol on the prevention of cardiac fibrosis.
封面
書名頁
口試委員會審定書
中文摘要............................................Ⅰ
英文摘要............................................Ⅲ
致謝................................................Ⅴ
目錄................................................Ⅵ
圖目錄..............................................Ⅶ
縮寫表..............................................Ⅹ
壹、緒論................................................1
心臟病與心臟纖維化......................................1
心臟纖維細胞............................................4
尿壓素..................................................5
厚朴酚..................................................8
實驗動機與目的..........................................9
貳、研究方法與材料.....................................11
參、結果...............................................24
尿壓素對於心臟纖維細胞的作用...........................24
厚朴酚對於心臟纖維細胞的作用...........................27
厚朴酚對於尿壓素所誘發心臟纖維細胞的作用...............29
肆、討論...............................................32
伍、結論與展望.........................................48
陸、圖表...............................................53
柒、參考文獻...........................................81
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