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研究生:李柏謙
研究生(外文):Po-Chien Lee
論文名稱:炭疽致死毒素在肝細胞中所造成不正常的凝血因子表現
論文名稱(外文):Anthrax lethal toxin induced abnormal coagulant factor expressions in hepatocytes
指導教授:張新侯
指導教授(外文):Hsin-Hou Chang
學位類別:碩士
校院名稱:慈濟大學
系所名稱:人類遺傳研究所
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:2005
畢業學年度:93
語文別:中文
論文頁數:57
中文關鍵詞:凝血因子致死毒素炭疽桿菌
外文關鍵詞:Anthraxlethal toxincoagulation factor
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炭疽桿菌可以孢子的形式潛伏在環境達數年之久,由於具有易散播與高致死率,可說是目前最致命的生化武器之一。炭疽毒素包含三種因子,如致死因子、致水腫因子與保護性抗原,當致死因子與致水腫因子和保護性抗原結合後,則會對人或動物造成嚴重性傷害,如出血與APTT、PT有延長情形,嚴重者會導致死亡,而致死因子與致水腫因子單獨存在則無任何功能。於先前研究中發現,在致死毒素感染老鼠模型中,老鼠因缺氧導致肝臟功能不正常,而肝臟又是最主要產生凝血因子的器官,故推測當人或動物受到炭疽感染,其凝血功能不正常,是由於凝血因子產生受到影響,進而造成出血嚴重症狀。根據本實驗初步結果,炭疽致死毒素會抑制肝癌細胞纖維蛋白原蛋白質生成,而在老鼠中則有血漿滲透與凝血因子不正常表現;且P-selectin與PSGL-1剔除老鼠模型中,則有提早死亡及凝血因子不正常表現。在凝血過程中,P-selectin扮演了重要角色,可幫助纖維蛋白沈澱、誘導組織因子微粒產生及促進血漿凝集,並可以恢復患有血友病A老鼠的凝血機制。因此目前在炭疽致死毒素所造成出血症狀,並無有效治療方式,故是否可以藉由P-selectin路徑來控制炭疽致死毒素所導致出血,恢復其凝血機制以利後續的治療,或許可以提供出血性疾病未來相關研究。
Anthrax is a disease of mammals, and it is caused by a spore-forming gram-positive Bacillus anthracis. It has been postulated to be a potential agent of biowarfare and bioterrorism. Anthrax toxin composed of three proteins called lethal factor (LF), edema factor (EF) and protective antigen (PA), each of which is nontoxic but acts synergistically. The combination of PA and LF, lethal toxin (LT), causes hemorrhage, death and prolongs clotting time. The effects of lethal toxin in mice were toxin-induced death not cytokine release, and it also caused hypoxia-induced liver failure. The liver is a major organ to produce coagulation factors. Hence, the coagulation factor expressions are abnormal when liver injure, and it causes abnormal hemostasis. We hypothesize that LT induce liver failure to cause abnormal coagulation factor expressions, and causes hemorrhage. We have showed that LT induced down-regulation of fibrinogen and abnormal coagulation factor expressions in human hepatoma cells, and it also induced plasma leakage and abnormal coagulation factor expressions in C57BL/6J mice. Similarly, LT induced early death and abnormal coagulation factor expressions in P-selectin and PSGL-1 knock-out mice. In previous studies, soluble P-selectin was observed to induce pro-coagulant state in mice, for example, to facilitate plasma clotting; in addition, it also been demonstrated to correct the hemostasis in hemophilia A mice and patients. There are no well therapies of anthrax induced hemorrhage in human. To further evaluate the P-selectin pathway to control anthrax lethal toxins induced hemorrhage, and correct the hemostasis.
1. 前言.............................................................1
2. 實驗材料與方法...................................................6
3. 實驗結果........................................................13
4. 討論............................................................19
5. 參考文獻........................................................23
6. 實驗結果圖表....................................................25
7. 附錄............................................................49
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