臺灣博碩士論文加值系統

臺灣為登革熱發生的高風險地區，然而我國目前沒有核准上市的疫苗或藥物，因此為重要的防疫問題。文獻指出紅藻水萃物具有抗氧化、抗發炎及免疫激活等效果。因此本研究旨在探討紅藻門的海木耳 (Sarcodia montagneana) 其水萃物對感染第二型登革病毒 (Dengue virus type 2, DENV2) 的保護效果。以熱水萃取法進行萃取，海木耳水萃物的產率為 60%，且經凝膠滲透層析儀 (Gel permeation chromatography, GPC) 分析，海木耳水萃物主要以 708 kDa 多醣及180 Da 單醣組成。細胞實驗利用 BHK-21 和DENV2 進行病毒斑抑制試驗 (Plaque reduction assay) 及定量即時聚合酶鏈鎖反應 (Quantitative real time polymerase chain reaction, q-PCR) 評估海木耳水萃物 (Sarcodia montagneana water extract, SMw) 是否能降低病毒量，體外實驗結果顯示，500 μg/mL 海木耳水萃物於預防 (Pre-treatment)、共培養 (Co-treatment) 及治療 (Post-treatment) 條件下分別有 93%、99% 及 55% 的病毒斑抑制率。感染組細胞內DENV2 NS5 表現量與時間成正比，而以預防、共培養及治療條件給予 SMw 可顯著降低細胞內DENV2 NS5 表現量，推測海木耳水萃物是藉由吸附宿主表面受器或病毒顆粒達到降低第二型登革病毒感染的效果。動物實驗部分，將 500 μg/mL 海木耳水萃物和 50 PFU 的 DENV2 共培養後，顱內感染十日齡 C3H/HeN 乳鼠可提升 50 % 的乳鼠存活率。另一方面，以預防條件於顱內感染前五日開始餵食海木耳水萃物，結果顯示，餵食5 mg 劑量的乳鼠相較於感染組可延長存活天數，臟器中病毒量也有顯著減少且具有減緩肝損傷的效果，由實驗結果推論，海木耳水萃物具有保護宿主且降低 DENV2 感染的效果。

Taiwan is a high-risk area where dengue fever occurs. However, there are no approved vaccines or drugs in Taiwan, so it is an important epidemic prevention problem. The literature indicate that the red algae water extract had anti-oxidation, anti-inflammatory and immune activation effects. Therefore, this study was aim to investigate the protective effect of the water extract of Sarcodia montagneana of Rhodophyta on the dengue virus type Ⅱ (DENV2) infection. Extracted by hot water extraction, the yield of Sarcodia montagneana water (SMw) extract is 60%. Use gel permeation chromatography (GPC) to analyze SMw, it was mainly comprise 708 kDa polysaccharide and 180 Da monosaccharide. In vitro, used baby hamster kidney-21 (BHK-21) cell and DENV2 for plaque inhibition assay and quantitative real-time polymerase chain reaction (q-PCR) to assess whether the SMw could reduce the virus burden. The results showed that the SMw (500 μg/mL) has 93%, 99%, and 55% plaque reduction rate in pre-treatment, co-treatment, and post-treatment condition, respectively. The expression of DENV2 NS5 gene in the virus group increased with time, while SMw significantly decreased the intracellular DENV2 NS5 gene expression in pre-treatment, co-treatment, and post-treatment condition. It was supposed that SMw could decrease the infection of DENV2 by absorbing the host surface receptor or virus particles. In vivo, intracranial infection of 10-day-old C3H/HeN suckling mice with mixture of 500 μg/mL SMw and DENV2 could increase the survival rate of 50%. Further, we administered 5 mg SMw on the 5th day before the intracranial infection, and the results showed that fed SMw could extend survival days. The virus load in organs was also significantly reduced and had the effect of improve liver injury. Those results showed that SMw had the effect of protect host and decrease DENV2 infection.

壹、 文獻回顧 1
一、 登革病毒 (Dengue virus) 1
1. 登革病毒之流行病學 1
2. 登革病毒之介紹 2
3. 登革病毒之生活史 5
4. 登革病毒感染之疾病病癥 6
5. 登革病毒躲避先天免疫 7
6. 登革病毒之處理和控制 8
二、 海木耳 (Sarcodia montagneana) 9
1. 海藻 (Red seaweed) 9
2. 紅藻 (Red seaweed) 9
3. 海木耳 (Sarcodia montagneana) 10
4. 海藻多醣抗病毒效果及其機制 10
貳、 實驗設計流程 14
一、 海木耳水萃物化學性質分析 14
二、 海木耳水萃物抗發炎及抗第二型登革病毒之體外試驗 14
三、 第二型登革病毒和海木耳水萃物共培養後之感染能力評估 15
四、 探討海木耳水萃物對第二型登革病毒感染的保護效果之體內試驗 15
參、 實驗材料與方法 16
一、 實驗材料 16
1. 樣品原料及萃取用有機溶劑 16
2. 化學性分析試驗 16
3. 標準品 16
4. 抗氧化試驗 16
5. 細胞株 17
6. 病毒株 17
7. 細胞培養之培養基 17
8. 細胞存活率試劑 17
9. 一氧化氮試驗 17
10. 病毒斑試驗 18
11. 實驗動物 18
12. RNA 萃取 18
13. 反轉錄反應試劑 18
14. 即時定量聚合酶連鎖試劑 19
15. 細胞激素分析 19
二、 儀器設備 19
三、 實驗方法 20
1. 實驗樣品製備 20
2. 海木耳水萃物化學特性分析 21
3. 登革病毒增殖培養 (Dengue virus amplify) 24
4. 細胞實驗 24
5. 動物實驗 29
6. 統計分析 31
肆、 結果 33
一、 海木耳水萃物化學性質分析 33
1. 海木耳水萃物產率與成分分析 33
2. 海木耳水萃物之總醣、硫酸根含量及抗氧化能力 33
二、 海木耳水萃物抗發炎及抗第二型登革病毒之體外試驗 33
1. 海木耳水萃物抗發炎能力評估 33
2. 海木耳水萃物對 BHK-21 之細胞毒性試驗 34
3. 海木耳水萃物抗第二型登革病毒效果之病毒斑抑制試驗 34
4. 海木耳水萃物於不同條件下對 DENV2 基因表現量之影響 34
三、 第二型登革病毒和海木耳水萃物共培養後之感染能力評估 35
1. 乳鼠外觀及行為之健康指數評分 35
2. 體內試驗評估共培養條件之第二型登革病毒的感染能力 35
四、 探討海木耳水萃物對第二型登革病毒感染的保護效果之體內試驗 36
1. 攝取海木耳水萃物對感染第二型登革病毒乳鼠的體重變化、健康指數及存活率之影響 36
2. 海木耳水萃物對感染第二型登革病毒乳鼠之生理影響 37
伍、 討論 40
一、 海木耳萃取與水萃物之化學性分析 40
二、 以體外試驗探討海木耳水萃物之生理活性 41
三、 以 C3H/HeN 乳鼠探討海木耳水萃物對感染 DENV2 之保護效果 42
陸、 結論 47
柒、 參考文獻 48
捌、 圖表 62

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