登革熱是由登革熱病毒所引起，藉由節肢動物媒介傳播的疾病，主要是埃及斑蚊和白線斑蚊。可引起登革熱或更嚴重的登革出血熱和登革休克症候群。熱帶和亞熱帶區為登革熱流行區域。目前沒有特殊藥物治療和疫苗可用，因此，登革熱是目前人類傳染性疾病中重要的疾病之一。為了有效控制和預防登革熱的傳播，快速定量的分子生物學方法對於登革熱的診斷是很重要的，目前分離登革熱病毒RNA的方法有很多種；然而新發展的磁硃方法尚未使用於分離登革熱病毒，因此論文第一部分為評估分離登革熱病毒RNA的方法，結果顯示分離登革熱RNA的最佳方法為人工法，而自動化的磁硃法和濾膜法並沒有顯著差異。除此，登革熱病毒所引起之登革出血熱是很嚴重的疾病，至今對於其致病機轉仍未完全了解，而臨床和實驗都有證實肝細胞為登革熱感染的目標細胞之一。因此本研究亦探討登革熱病毒感染肝細胞後的細胞凋亡機制，一些研究顯示登革熱急性期會引起自由基產生和抗氧化狀態的改變，而p21是細胞週期調控因子，有報告指出其在細胞凋亡中扮演重要的角色，所以本論文第二部分乃探討自由基和p21在登革熱病毒感染肝細胞凋亡中所扮演的角色。結果顯示在登革熱病毒感染HepG2細胞後，p21 mRNA表現量會有增加的情形，而抗氧化劑 NAC、GSH、DPI 均能抑制細胞凋亡及p21 mRNA的表現，然而p21的表現是否和細胞凋亡有關，需要更進一步的探討。

Dengue fever is an arthropod-borne transmit disease, caused by dengue virus.The principal vectors are Aedes aegypti and Aedes albopictus. Induce Dengue fever (DF) and a more severe form of dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS). Dengue virus is the most prevalent arbovirus in tropical and subtropical regions. There is no specific drug and vaccine available for treatment and prevention. Therefore, DF is an important disease among transmit diseases in humans. For the effective control and prevention of DF transmission, rapid quantitative molecular biological methods are very important for the diagnosis of dengue fever. At present, there are many methods to isolate the RNA of Dengue virus; however, the new developed magnetic method has not been used for the Dengue virus isolation yet. At first, we evaluated various methods for Dengue virus isolation. The result indicate that the best method of RNA extraction for dengue virus is the QIAamp® Viral RNA kit manual extraction. There are no apparent differences of the effect for Dengue virus RNA isolation between filting film and magnetic bead method. Furthermore, DHF caused by Dengue virus is a very serious disease and the pathologic mechanism of DHF has not been elucidated completely. Both clinical and experimental trials have confirmed that the liver cell is one of the target infected by Dengue virus. And, the mechanism of Dengue virus-induced liver cell apoptosis remains poorly understood.Furthermore, there are free radical and cytokines production in patient，s serum in the acute phase of DF. Therefore, the role of antioxidant and p21 in the mechanisms should be elucidcited. Our preliminary data show that p21 mRNA expression increase in HepG2 after Dengue virus infection. NAC, GSH, and DPI all can attenuate Dengue-induced cell apoptosis. Howerer, the relationship between p21 expression and liver cell apoptosis should be further clarified in the near future.

中 文 摘 要....... I
Abstract..........III
圖 目 錄.......... VI
表 目 錄..........VII
緒 論............1
材 料 與 方 法....17
討 論............41
參 考 文 獻....... 45

台北市內湖區健康中心防疫資訊
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