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系統識別號 U0026-0812200911544181
論文名稱(中文) 乳鐵蛋白、芝麻油或芝麻酚對泛抗藥性不動桿菌感染的保護作用
論文名稱(英文) Protective effects of lactoferrin, sesame oil, or sesamol on the infection of pandrug-resistant Acinetobacter baumannii
校院名稱 成功大學
系所名稱(中) 醫學檢驗生物技術學系碩博士班
系所名稱(英) Department of Medical Laboratory Science and Biotechnology
學年度 94
學期 2
出版年 95
研究生(中文) 廖淑杏
研究生(英文) Susan Liao
學號 t3692109
學位類別 碩士
語文別 中文
論文頁數 91頁
口試委員 口試委員- 劉明毅
指導教授-葉才明
口試委員-張長泉
中文關鍵字 乳鐵蛋白  芝麻油  芝麻酚  泛抗藥性不動桿菌 
英文關鍵字 lactoferrin  sesame oil  sesamol  pandrug-resistant Acinetobacter baumannii 
學科別分類
中文摘要 鮑氏不動桿菌(Acinetobacter baumannii)為ㄧ個革蘭氏陰性球桿菌常見於新鮮的水及土壤中,A. baumannii也是院內感染性肺炎的致病菌,主要出現在使用氣管插管或輔助性呼吸器或具有潛在性肺炎疾病的病人身上。因為現在市場上所使用的抗生素大都無效,所以發展出新的策略來治療這些病人是重要的。乳鐵蛋白(lactoferrin)是一個會與鐵結合的醣蛋白,分子質量為80萬,乳鐵蛋白具有抗微生物及免疫增強的雙重作用。芝麻酚(sesamol)是芝麻油(sesame oil)的主要成分,具有很強的抗發炎及抗氧化的效應。在本研究中,我們使用了生長曲線從體外(in vitro)來看乳鐵蛋白及芝麻酚對於A. baumannii的生長影響;另外我們利用老鼠的存活率、肝腎生化指標、肝腎組織切片及細胞激素的產生,從體內(in vivo)經A. baumannii感染的老鼠模式中探討乳鐵蛋白、芝麻油及芝麻酚對A. baumannii感染所能發揮的保護效果。我們發現使用乳鐵蛋白可以隨著其劑量而增強對A. baumannii在體外生長的抑制,但此種現象當我們改為芝麻酚就看不到了。此外以乳鐵蛋白、芝麻油或芝麻酚來治療比未治療的老鼠有較高的存活率及較低的肝臟及腎臟器官傷害並且可以降低老鼠血液中TNF-的生成。因此,乳鐵蛋白、芝麻油或芝麻酚具有降低A. baumannii感染所造成的傷害,三者之間似乎有著不同的機制來達到治療的效果。

英文摘要 Acinetobacter baumannii is a gram negative coco-bacillus, which is ubiquitous present in fresh water and soil. A. baumannii is also a well recognized pathogen causing nosocomial pneumonia, predominantly in patients with endotracheal intubation, prolonged mechanical ventilation, and underlying lung diseases. Because almost all commercially available antibiotics are ineffective against A. baumannii, it is necessary to develop a new strategy to treat infections caused by A. baumannii. Lactoferrin (LF) is an iron-binding glycoprotein with a molecular mass of 80 KDa. Lactoferrin is present in milk, saliva, mucous secretion, and other biological fluids of mammals. LF has both anti microbial and immune modulating/enhancing ac-tivities. Sesamol (SM) is a main component of sesame oil (SO) and it has po-tent anti-inflammatory and antioxidant activities. In this study, the effects of LF, SO, and SM on a mouse infection model of A. baumannii were investigated. It was found that treatment with LF, SO, and SM could protect mice from A. baumannii-induced lethality. The results revealed higher survival rate, lower liver and kidney damage and decreased serum TNF-a production in mice treated with LF, SO, or SM than the control mice. Furthermore, the growth of A. baumannii was inhibited in the presence of LF in vitro, but in vitro inhibition is not seen in the presence of SM. Therefore, LF, SO, and SM may have protective effects against A. baumannii infection through different mechanisms.

論文目次 總 目 錄
中文摘要 1
英文摘要 2
誌謝 3
總目錄 4
圖目錄 9
表目錄 10
緒論 11
一、鮑氏不動桿菌(A. baumanni) 11
(一) A. baumannii的感染方式 11
(二) A. baumanni的抗藥性 12
(三)多重抗藥性A. baumanni的感染 13
(四)多重抗藥性A. baumanni感染的治療方法 14
(五)多重抗藥性A. baumanni感染動物研究模式 15
二、A. baumannii造成的敗血性休克 17
(一) 敗血症的流行病學 17
(二) 敗血症的感染 18
(三) 敗血症早期發炎細胞激素 18
3-1細胞介白素(Interleukin)-1 (IL-1) 18
3-2 腫瘤壞死因子(tumor necrosis factor ,TNF-) 19
(四) 敗血症的療法 19
三、乳鐵蛋白(Lactoferrin; LF) 21
(一)結構及特性 21
(二)乳鐵蛋白的生物特性 22
1. 乳鐵蛋白與鐵的運輸及與吸收之關係 22
2. 乳鐵蛋白的免疫調節功能 23
3. 乳鐵蛋白的抗氧化作用 24
4. 乳鐵蛋白的抗癌作用 25
5. 乳鐵蛋白可促進細胞生長 25
6. 乳鐵蛋白具有抗病毒功能 26
7. 乳鐵蛋白的抗菌功能 27
四、芝麻油 28
(一) 芝麻油的功用 29
1. 抗癌作用 29
2. 抗病毒 29
3. 抗發炎 30
(二) 芝麻酚(sesamol) 30
研究目的與動機 33
研究材料與方法 34
一、材料 34
(一) 儀器 34
(二) 試劑藥品暨耗材 37
二、實驗方法 40
(一) 菌株來源 40
1-1瓊脂紙錠稀釋試驗(disc diffusion method) 40
1-2抗生素濃度梯度梯度E test試紙條(E test) 40
(二) 細菌單菌落分離與菌液之培養 41
2-1單一菌落(single colony)之分離 41
2-2菌液(bacterial suspension culture)之培養 41
(三) 聚合酵素連鎖反應 (polymerase chain reaction;PCR) 41
3-1 PCR產物確認 42
3-2 PCR產物純化 43
3-3 PCR產物定序 44
3-4 序列分析 44
三、動物處理 45
(一) 動物飼養 45
(二) 腹腔注射(intraperitoneally, i.p) 45
四、血液樣本收集 46
五、病理切片 46
六、測量項目 46
(一) 血液生化分析 46
(二) 不同劑量的芝麻油或芝麻酚對A. baumannii誘導肝腎功能
異常的影響 47
(三) 細胞激素之測定 47
七、統計分析 48
結果 49
一、A. baumannii菌株的序列分析 49
二、抗生素(IPM)及乳鐵蛋白抑制A. baumannii的生長效果 49
(一) 乳鐵蛋白(LF)對A. baumannii的抑菌效果 50
(二) 比較乳鐵蛋白(LF)單獨或合併使用抗生素(IPM)下對
A. baumannii的抑菌效果 51
(三) 抗生素(IPM)及乳鐵蛋白(LF)在不同時間點抑制
A. baumannii生長的情形 52
三、芝麻酚(SM)抑制A. baumannii的生長效果
四、乳鐵蛋白(LF)、芝麻油(SO)及芝麻酚(SM)對於老鼠存活率
的影響 52
(一) A. baumannii感染後老鼠的存活率 53
(二) 乳鐵蛋白作用下A. baumannii感染老鼠的存活率 53
(三) 芝麻油作用下A. baumannii感染老鼠的存活率 54
(四) 芝麻酚作用下A. baumannii感染老鼠的存活率 55
四、生化指標 56
(一) 肝功能 56
(二) 腎功能 56
五、乳鐵蛋白(LF)、芝麻油(SO)及芝麻酚(SM)對於A. baumannii感
染後老鼠組織切片的影響 57
(一) 肝臟細胞的保護情形 57
(二) 腎臟細胞的保護情形 57
六、乳鐵蛋白(LF)、芝麻油(SO)及芝麻酚(SM)對於A. baumannii感
染後老鼠血清中細胞激素的影響 58
討論 60
(一)為何乳鐵蛋白可以造成抗生素(IPM)的作用加強? 60
(二)乳鐵蛋白(LF)及芝麻酚(SM)在體外抑制A. baumannii的生長效果
(三)乳鐵蛋白(LF)在A. baumannii感染老鼠上的研究 61
(四)芝麻油(SO)及芝麻酚(SM)在A. baumannii感染老鼠上的研究62
(五)早期的細胞激素的產生 62
參考文獻 65
附錄(實驗設計) 90
自述 91
圖 目 錄
圖一:A. baumannii的序列分析
圖二:不同劑量的乳鐵蛋白(LF)對A. baumannii生長的影響
圖三:抗生素(IPM)及乳鐵蛋白(LF)在不同時間點抑制A. baumanni生長的
情況
圖四:不同劑量的抗生素(IPM)及乳鐵蛋白(LF)抑制A. baumannii生長的效

圖五:不同接種量的A. baumannii對老鼠存活率的影響
圖六:抗生素(IPM)及乳鐵蛋白(LF)對接種A. baumannii老鼠存活率的影響
圖七:不同劑量的芝麻油(SO)對於接種A. baumannii老鼠存活率之影響
圖八:芝麻酚(SM)在不同時間點抑制A. baumannii株生長的情況
圖九:芝麻酚(SM)在不同濃度下對A. baumannii感染老鼠存活率的影響
圖十:乳鐵蛋白(LF)、芝麻油(SO)及芝麻酚(SM)對於A. baumannii感染後老鼠
生化指標的影響
圖十一:乳鐵蛋白(LF)、芝麻油(SO)及芝麻酚(SM)對A. baumannii感染後老鼠
的肝臟組織切片影響
圖十二:乳鐵蛋白(LF)、芝麻油(SO)及芝麻酚(SM)對A. baumannii感染後老鼠
的腎臟組織切片影響
圖十三:A. baumannii感染老鼠及芝麻油 (SO) 或芝麻酚(SM) 處理後TNF-
表現的分析

表 目 錄
表一: IPM及LF單獨及合併使用對老鼠感染A. baumannii存活率的影響
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