請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55878
標題: | 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 Role of neutrophil extracellular traps in the bacterial colonization and vegetation formation in oral streptococci-induced infective endocarditis |
作者: | Han-Yuan Liu 劉瀚遠 |
指導教授: | 賈景山 |
關鍵字: | 嗜中性白血球,口腔鏈球菌,心內膜炎, neutrophil,oral streptococci,infective endocarditis, |
出版年 : | 2014 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55878 |
全文授權: | 有償授權 |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 3.01 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。