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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賈景山 | |
dc.contributor.author | Han-Yuan Liu | en |
dc.contributor.author | 劉瀚遠 | zh_TW |
dc.date.accessioned | 2021-06-16T05:10:00Z | - |
dc.date.available | 2019-10-09 | |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-19 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55878 | - |
dc.description.abstract | 感染性心內膜炎(infective endocarditis)目前在臨床上仍具有高致死率以及高復發率,常由口腔中共生之鏈球菌(如轉糖鏈球菌及戈登鏈球菌)所引發,這些口腔中的病原菌可在受損的心臟瓣膜上形成生物膜,並與血小板(platelet),發炎細胞以及纖維蛋白( Fibirn )共同堆疊形成贅疣(vegetation),進而產生感染性心內膜炎。研究已發現嗜中性球胞外網狀結構(neutrophil extracellular traps, NETs)可抓住並活化血流中的血小板並促進血栓的形成。目前實驗室的研究顯示NETs的生成在轉糖鏈球菌所引起的生物膜以及贅疣形成過程中扮演一定的角色,也導致細菌對於抗生素的抗藥性。因此,若破壞NETs的結構,應有助於降低受損瓣膜上鏈球菌落的增長。本次研究以感染性心內膜炎大鼠模式中分別評估以預防性及治療性給予bovine DNase I的效果。觀察到bovine DNase I的的確能降低贅疣的大小,但同時也增加了血液中游離的細菌。以抗生素搭配bovine DNase I的情況下可顯著地降低贅疣中細菌數目以及血液中的菌量。另外,額外添加以Aspirin抑制血小板活化,能夠增加周邊血流以及內臟組織中細菌的清除效果。同樣的,以預防性注射給予戈登鏈球菌感染的心內膜炎大鼠能夠減少贅疣大小以及其上細菌生物膜的生成。因此,將NETs作為新的藥物標的應可有做為一個有效控制感染性心內膜炎疾病的治療方式。 | zh_TW |
dc.description.abstract | Infective endocarditis (IE), a cardiovascular infectious disease, remains a high mortality rate and is usually caused by oral streptococci (such as Streptococcus mutans and Streptococcus gordonii). These streptococci can adhere to the injured valve and form vegetation, a compact fibrin-platelet bacterial biofilm, to cause IE. Neutrophil extracellular traps (NETs) can trap and activate the circulating platelets and induce the blood clot formation. This study test the hypothesis that the NETs formation plays a role in the Streptococcus mutans-induced biofilm and vegetation formation, which contribute to the bacterial antibiotic resistance. Therefore, disruption of NETs may help the antibiotics to reduce the streptococcal colonization on the injured valve. The experimental endocarditis rat model was used to evaluate the prophylactic and therapeutics effect of bovine DNase I, and found that bovine DNase I could significantly reduce the size of vegetation but enhance the circulating bacteria. Administration of bovine DNase I in combination with antibiotics could dramatically reduce the size of vegetation, the number of colonized bacteria and circulating bacteria. Addition of the platelet activation inhibitor, aspirin, could enhance the bacteremia clearance in tissues and in the circulation. Consistently, prophylaxis of DNase I could inhibit S. gordonii biofilm and vegetation formation in vivo. Therefore, targeting at NETs may provide a new strategy for controlling IE. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:10:00Z (GMT). No. of bitstreams: 1 ntu-103-R01445119-1.pdf: 3080945 bytes, checksum: 23a2ba5785d1d324a5b2c2089939ded5 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員審定書 i
致謝 ii 中文摘要 iii Abstract iv 壹、緒論 1 一、轉糖鏈球菌( S. mutans )與戈登鏈球菌(S. gordonii) 1 二、菌血症(Bacteremia) 3 三、生物膜(biofilm) 4 四、嗜中性白血球(Neutrophil) 5 五、嗜中性白血球胞外網狀結構(neutrophil extracellular traps,NETs) 6 六、研究目的 7 貳、實驗材料與方法 9 一、轉糖鏈球菌之培養 9 二、鏈球菌之轉型作用 9 三、細菌處理及感染方式 9 四、實驗性心內膜炎之老鼠模式的建立 10 五、以藥物降低感染性心內膜炎大鼠瓣膜贅疣上嗜中性白血球胞外網狀結構 10 1. 藥物配置及給予大鼠之方法 10 2. 定量血液中鏈球菌菌數之方法 11 3. 定量贅疣上鏈球菌菌數之方法 11 4. 定量組織中上菌數之方法 11 5. 偵測血流中NETs存在之方法 12 六、觀察感染性心內膜炎贅疣中NET的方法 12 七、人類嗜中性白血球之分離及純化 13 參、結果 14 第一部份、嗜中性白血球胞外網狀結構對於抗生素殺菌效果的影響 14 第二部分、DNase I對於大鼠心內膜炎贅疣上NETs的清除效果 14 第三部分、抗生素搭配bovine pancreatic DNase I 對大鼠在轉糖鏈球菌感染性心內膜炎中的預防性效果 16 第四部份、抗生素搭配bovine pancreatic dnase I 對大鼠在轉糖鏈球菌感染性心內膜炎中的治療性效果 18 第五部分、抗生素搭配bovine pancreatic DNase I 對大鼠在戈登鏈球菌感染性心內膜炎中的影響效果 19 肆、討論 20 一、嗜中性胞外網狀結構的釋放與細菌生物膜 20 二、抗生素以及血小板活化對於細菌生物膜的影響 20 三、周邊臟器中NET的產生以及菌血症的關聯性 22 四、戈登鏈球菌於大鼠心內膜炎感染中的清除 23 五、DNase I是否對於受損瓣膜處發炎反應的調控有所影響 23 六、結論 25 伍、參考文獻 26 陸、附圖 31 圖表目錄 圖一、於體外環境刺激人類嗜中性白血球釋放胞外網狀結構並共同培養轉糖鏈球菌並觀察其菌量分布與變化 33 圖二、Bovine DNase I的注射對於心內膜炎中贅疣以及周邊血流中的 35 圖三、預防性藥物注射對於轉糖鏈球菌感染性心內膜炎大鼠實驗流程設計 36 圖四、感染轉糖鏈球菌前三十分鐘預防性注射對於瓣膜贅疣以及周邊菌血症影響 39 圖五、感染前三十分鐘預防性性注射對贅疣上NETs的分布以及抑制轉糖鏈球菌生物膜的影響 40 圖六、治療性藥物注射對於轉糖鏈球菌感染性心內膜炎大鼠實驗流程設計 41 圖七、感染轉糖鏈球菌後四小時以治療性注射對於瓣膜贅疣以及周邊菌血症影響 44 圖八、 感染轉糖鏈球菌四小時後治療性注射對贅疣上NETs的分布以及抑制轉糖鏈球菌生物膜的影響 45 圖九、以DNase I對於戈登鏈球菌進行感染前30分鐘預防性注射搭配抗生素對於 瓣膜贅疣上生物膜分布以及周邊血液及組織中戈登鏈球菌菌量的影響 48 | |
dc.language.iso | zh-TW | |
dc.title | 嗜中性白血球胞外網狀結構在口腔鏈球菌引發心內膜炎細菌附著以及贅疣形成的角色 | zh_TW |
dc.title | Role of neutrophil extracellular traps in the
bacterial colonization and vegetation formation in oral streptococci-induced infective endocarditis | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 符文美,陳文彬,林君榮 | |
dc.subject.keyword | 嗜中性白血球,口腔鏈球菌,心內膜炎, | zh_TW |
dc.subject.keyword | neutrophil,oral streptococci,infective endocarditis, | en |
dc.relation.page | 48 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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