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研究生:葉力仁
研究生(外文):Li-Jen
論文名稱:台灣佳葉龍茶(GABA tea)萃取液抗先天性高血壓大白鼠(SHR)心肌凋亡分子機轉探討
論文名稱(外文):Molecular Mechanisms of Antiapoptotic Effects of GABA Tea on Spontaneously Hypertensive Rat (SHR) Hearts
指導教授:蔡淦仁
指導教授(外文):Kan-Jen Tsai
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:生化暨生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:76
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心肌細胞凋亡是造成心臟衰竭的主因。實驗的目的在探討台灣佳葉龍茶(GABA tea)萃取液抗先天性高血壓大白鼠(SHR)心肌凋亡之分子機轉。我們採用雄性八週齡先天性高血壓大白鼠,約200公克,經適應五週後分成六組,每組5-6隻動物。並將此六組先天性高血壓大白鼠分別餵食水(water/20ml/day/rat)、高劑量(301μgGABA/extracting tea/20ml/day/rat) 佳葉龍茶(HGT)、低劑量(151μgGABA/extracting tea/20ml/day/rat)佳葉龍茶湯(LGT)、高(301μgGABA/20ml/day/rat) 純GABA溶液(HG)與低(151μgGABA/20ml/day/rat)純GABA溶液(LG)及綠茶湯(20ml/day/rat)(GT)。所有動物,均採自由攝食飼料與實驗樣品12週,再進一步探討與心肌細胞凋亡及存活等相關路徑。我們首先從H&E 染色的心臟切片中發現GABA和green tea有減緩SHR心肌細胞傷害的情形。並在TUNEL assay中觀察到GABA和green tea具可抑制SHR產生的心肌細胞凋亡的情形。進一步採用Western Blot分析,發現SHR心肌細胞凋亡,同時透過Death receptor dependent及Mitochondria dependent這兩條路徑。而GABA和green tea不僅具抑制此兩條凋亡路徑之作用,同時活化了IGF-I及PI3K/Akt心肌存活路徑來保護SHR的心肌細胞且以上的作用均以LG及GT為佳。由以上的研究結果,使我們相信適量的GABA及green tea均具有保護心肌細胞的作用。相信適量的GABA及green tea給予,應可降低高血壓治療用藥的劑量和依賴程度。

Background:Cardiomyocytes apoptosis is the major risk factor for the development of heart failure (HF). The purpose of this study was to evaluate the effects of GABA tea on hypertension induced cardiac apoptotic pathways in SHR. Methods: In order to reveal the mechanisms, thirty-six male spontaneously hypertensive rats (SHR) at eight weeks of age, 200g were divided into six groups .One group was fed water as a background control group.other rats were administered one of the following treatments: GABA tea at dose 150 and 300 mg/kg BW as LGT and HGT groups,respectively, pure GABA at dose 150 and 300 mg/kg BW as LG and HG groups,respectively , green tea(GT) as control of LGT and HGT groups. After 12 weeks,cardiac tissues were analyzed by histological analysis, western blotting and TUNEL assays. Results: GABA tea, green tea and pure GABA ,decreased hypertension -induced cardiac abnormalities,including abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive apoptotic cells. In addition,GABA tea ,green tea and pure GABA, decreased protein levels of Fas ligand, Fas death receptors,FADD,Bax and Bak, and dramatically increased anti-apoptotic proteins ,Bcl2.Further more GABA tea green tea and pure GABA also decreased activated-Caspase8,activated-caspase 9 and activated-caspase 3. Additionally, the expressions of IGF-I and PI3K/Akt pathway, maintaining the survival to cardiomyocytes were also upregulated.All of the above result , LG and green tea anti-apoptotic and pro-survival effects showed the best. Conclusion: The cardioprotective effect of GABA tea green tea and pure GABA can be attributed to not only antioxidant and antihypertensive properties but also improvement of the cardiomyctye apoptosis by induced hypertension .

中文摘要 1
Abstract 2
壹、緒論 3
貳、背景介紹 10
参、研究動機 28
肆、實驗方法 29
伍、實驗材料 35
陸、結果 40
柒、討論 48
捌、參考文獻 54
圖表 62


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