臺灣博碩士論文加值系統

心血管疾病的死亡率在現代化社會中一直是居高不下，而在衛生署每年所公佈的十大死因中也是名列前矛，因此心血管疾病的治療與預防在未來是相當重要及必須重視的課題。Doxorubicin是一種用來治療癌症的藥物，但在長期的使用下，會產生大量的ROS而造成心臟的損傷，因此大大的限制了此種藥物的使用。山藥在台灣是常見的食物及食材，而在本實驗室先前的研究發現，短期服用可增加血清中NO、cGMP、抗氧化能力及表現於心臟中磷酸二酯解酶(Phosphodiesterases；PDE)酵素的活性。因此本研究以不同種山藥水萃物及酒萃物餵食BALB/C小鼠連續8週，於第5週時，注射Doxorubicin(15mg/kg body weight)，每週一次連續4週使其誘發心臟損傷，接著取其心臟與血清進行實驗分析，觀察山藥是否可有效改善Doxorubicin所造成的心臟損傷。結果顯示在預先餵食不同種的山藥萃取物8週後，可增加心臟的抗氧化酵素能力，降低心臟中發炎因子NF-κB；TGF-β的表現量，改變心臟中cGMP、cAMP的表現量及心臟中PDE3a、PDE5a的活性。因此根據本研究結果顯示山藥萃取物可透過降低體內的氧化壓力、發炎作用及改變PDE的表現量，將有助於減緩Doxorubicin所造成的心臟損傷及一般心血管疾病之改善。

Doxorubicin is a medicine for cancer therapy; however, it causes cardiac damage via massive production of reactive oxygen species (ROS). Yam is common plant food in Taiwan. Our previous study found that yam could increase NO, cGMP, anti-oxidative activity and phosphodiesterases (PDE) activity in heart of mice. Therefore, in present study, BALB/C mice were supplied eight weeks with water extract of yam or alcohol extract of yam, and followed by doxorubicin treatment (15 mg/kg body weight) once a week for four weeks. Heart and serum were collected. Results showed that two different yam extracts intake increased anti-oxidative enzyme activity in heart, decreased the expression of inflammatory factors, NF-κB and TGF-β, changed the expression and/or activity of cGMP, cAMP PDE3a and PDE5a in heart. Theses findings suggest that yam extract could alleviate cardiac damage caused by doxorunicin via decreasing oxidative stress, inflammatory injury and affecting PDE expression.

目錄.....................................................................................................................I
圖表目次...........................................................................................................III
中文摘要...........................................................................................................IV
英文摘要...........................................................................................................V
第一章、 前言....................................................................................................1
第二章、 文獻探討............................................................................................3
一、 山藥.........................................................................................................3
二、 艾黴素 (Doxorubicin：Dox)....................................................................4
三、 環狀單磷酸鳥糞嘌呤＆環單磷酸腺苷
(cyclic guanosine3’,5’-monophosphate：cGMP) ＆
(cyclic adenosine3’,5’-monophosphate：cAMP).....................................6
四、 第三型磷酸二酯解酶(Type 3 Phosphodiesterases：PDE3).....................7
五、 第五型磷酸二酯解酶(Type 5 Phosphodiesterases：PDE5).....................8
六、 乳酸脫氫酶(Lactate dehydrogenase：LDH).............................................9
七、 抗氧化系統............................................................................................10
第三章、 研究目的..........................................................................................11
第四章、 材料與方法......................................................................................12
一、 實驗材料...............................................................................................12
(一) 實驗原料.........................................................................................12
(二) 實驗動物.........................................................................................12
(三) 化學藥品.........................................................................................12
(四) 儀器設備.........................................................................................13
二、 實驗方法................................................................................................14
(一) 山藥萃取物飼料製備.....................................................................14
(二) 心毒性Balb/c小鼠模式..................................................................14
(三) 實驗動物.........................................................................................14
(四) 實驗設計.........................................................................................15
(五) 血液及臟器收集.............................................................................15
三、 實驗分析................................................................................................16
(一) 心跳(HR)及血壓(BPs)....................................................................16
(二) 乳酸脫氫酶(LDH)..........................................................................16
(三) 環狀單磷酸鳥糞嘌呤(cGMP)測定................................................17
(四) 環單磷酸腺苷(cAMP)測定............................................................17
(五) 總蛋白質(Total protein)濃度之測定..............................................18
(六) 麩胱苷肽(Glutathione；GSH)濃度測定..........................................19
(七) 麩胱苷肽過氧化酶(Glutathione Peroxidase；GPx) 活性測定....20
(八) 脂質過氧化 (Malondialdehyde；MDA)測定.................................21
(九) 腫瘤壞死因子(Tumor Necrosis Factor-α；TNF-α).........................22
(十) protein kinase A 之西方墨點法（Western blot）.....................22
(十一) 反轉錄聚合酶連鎖反應.................................................................23
(十二) 統計分析.........................................................................................26
第五章、 實驗結果...........................................................................................27
(一) 以Dox誘發心毒性小鼠之動物模式特徵.................................27
(二) 餵食不同山藥萃取物對心毒性小鼠體內血清、心臟生化數值
的影響........................................................................................32
(三) 餵食不同山藥萃取物對心毒性小鼠體內心臟氧化壓力的影
響................................................................................................36
(四) 餵食不同山藥萃取物對心毒性小鼠體內發炎反應的影響.....40
(五) 餵食不同山藥萃取物對心毒性小鼠體內心臟磷酸二酯解酶基
因表現磷酸化蛋白激酶（protein kinase a）蛋白表現量............44
第六章、 討論..................................................................................................48
﹙一﹚ 山藥萃取物對小鼠生理作用的影響.........................................48
﹙二﹚ 山藥萃取物對細胞受損的影響.................................................48
﹙三﹚ 山藥萃取物對抗氧化系統的影響.............................................49
﹙四﹚ 山藥萃取物對發炎反應的影響.................................................49
﹙五﹚ 山藥萃取物對cGMP、cAMP及PDE酵素的影響.....................49
﹙六﹚ 综合討論.....................................................................................50
第七章、 結論..................................................................................................53
第八章、 文獻參考..........................................................................................54

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