臺灣博碩士論文加值系統

登革病毒 (dengue virus, DENV) 主要藉由病媒蚊傳播感染至人體內，其感染後可能會引起登革熱 (dengue fever, DF)，或是更嚴重的疾病如：登革出血熱/登革休克症候群 (dengue hemorrhagic fever/ dengue shock syndrome, DHF/DSS)。然而免疫系統較差與第二次感染登革病毒的人其可能更容易造成登革出血熱。本實驗以7種中草藥對登革病毒的影響進行探討，結果發現中草藥51與牛樟芝共同發酵物 (AC-CH51) 相較於單獨牛樟芝發酵物 (AC) 可減少病毒斑之形成，並且降低由DENV2誘導的細胞死亡。AC-CH51以DENV2感染前處理細胞可提高抗病毒的效果，在此顯示AC-CH51的抗病毒的作用，可能一部份可與細胞相互作用以影響DENV2吸附於細胞上。進一步以DENV2感染動物模式證實於感染前3天餵食AC-CH51可降低血球比容、減緩血小板低下與腸胃道出血情形，並且可提高感染小鼠之存活率。此外，在免疫不全的小鼠 (neonatal mice) 中發現AC-CH51可增強前發炎與抗病毒細胞激素iNOS、IL-1β、IFN-β之表現，也可降低由LPS誘導RAW264.7之一氧化氮產量。於我們目前的研究顯示，AC-CH51可能有助於增強抗登革病毒感染的臨床結果。

Dengue viral infections are one of the most important mosquito borne diseases in the world. They may give rise to dengue fever (DF) or severe illness dengue hemorrhagic fever (DHF). People with weakened immune systems or those with a second or subsequent dengue infection are believed to be at greater risk for developing dengue hemorrhagic fever. Herein, 6 kinds of Chinese herbs (CH) were chosen, and their effects on the anti-dengue virus were investigated. We found that the co-fermentation of the CH51 with Antrodia cinnamomea (AC-CH51) showed better reduction of plaque formation as well as an decrease in the DENV2-induced cell death, compared to the fermentation of the Antrodia cinnamomea (AC) alone. Interestingly, their efficiency was significantly increased by pre-treating cells. This suggests that the anti-viral effect by AC-CH51, in part, by the interference of virus adsorption. We further demonstrated that AC-CH51 attenuates hematocrit, thrombocytopenia and gastrointestinal bleeding, and improves survival rate in neonatal mice after virus infection. Moreover, this fermentation enhances pro-inflammation and anti-viral cytokines (iNOS, IL-1β, IFN-β) expression in immunodeficient hosts (neonatal mice), whereas reduces LPS-induced NO production in RAW264.7. Notice on issuing of contravention indicates that AC-CH51 may have an immunomodulatory effect against virus infection. Consequently, given our present findings, we propose that the AC-CH51 may contribute to the enhancement of clinical outcomes against dengue viral infection.

目錄 I
表目錄 IV
圖目錄 V
中文摘要 VI
Abstract VII
第一章 緒論 1
壹、登革病毒 (Dengue virus) 1
一、登革病毒之流行病學 1
二、登革病毒之簡介 1
三、登革病毒之生活史 3
四、登革病毒感染之疾病病徵 3
1. 登革熱 3
2. 登革出血熱/登革休克症候群 4
五、登革病毒之預防與治療 4
貳、中草藥 (Chinese herbs) 5
一、中草藥的研究與發展現況 5
二、中草藥之功效 5
參、牛樟芝 (Antrodia cinnamomea) 6
一、牛樟芝介紹 6
1. 牛樟芝的命名 7
2. 牛樟芝之分類學 7
3. 牛樟芝的型態與生長環境 7
二、牛樟芝生理活性成份 8
1. 多醣體 (Polysaccharides) 8
2. 三萜類化合物 (Triterpenoids) 8
三、牛樟芝之功效 8
1. 抗氧化 9
2. 抗發炎 9
3. 抗癌 9
4. 抗菌、抗病毒 9
5. 保護肝臟 10
6. 免疫調節 10
7. 調節血糖、血脂 10
肆、實驗目的 11
第二章 實驗材料與方法 12
壹、實驗材料 12
貳、儀器設備及分析軟體 16
參、實驗方法 16
一、牛樟芝-中草藥發酵產物一般成分分析 16
1. 水分含量測定 16
2. 灰份含量測定 16
3. 粗蛋白含量測定 16
4. 總醣含量測定 17
5. 硫酸根含量 17
二、細胞實驗 17
1. 細胞培養 17
2. 登革病毒產生方式 18
3. 登革病毒效價測定 18
4. 細胞毒性試驗 (MTS assay) 19
5. 牛樟芝-中草藥發酵物對於登革病毒感染之影響 19
三、動物實驗 23
1. 腸胃道出血觀察 23
2. 組織中病毒之病毒效價測定 23
3.偵測組織中病毒蛋白及細胞激素RNA表現量 24
4. 偵測組織中病毒蛋白質表現量 25
5. 組織病理切片 26
6. 血液分析 27
四、統計分析 27
第三章 結果 28
壹、七種中草藥萃取物對於抗登革病毒感染之in vitro試驗 28
一、單獨牛樟芝發酵物及中草藥對於BHK-21之細胞毒性試驗 28
二、牛樟芝-中草藥發酵物對於BHK-21之細胞毒性試驗 28
三、單獨牛樟芝發酵物及中草藥對於抗第二型登革病毒感染之能力 28
四、牛樟芝-中草藥發酵物對於抗第二型登革病毒感染之能力 28
五、抑制病毒斑生成 29
六、降低胞內登革病毒非結構性蛋白NS3表現 29
七、降低胞內病毒抗原之表現 29
貳、牛樟芝發酵物與牛樟芝-中草藥發酵物之成分分析 30
參、牛樟芝-中草藥發酵物對於登革病毒感染乳鼠之影響 30
一、感染前3天餵食牛樟芝-中草藥發酵物之感染乳鼠保護效果評估 30
二、登革臨床症狀之觀察 30
三、感染前3天餵食牛樟芝-中草藥發酵物之乳鼠各組織NS3表現 31
四、感染前3天餵食牛樟芝-中草藥發酵物之乳鼠組織中病毒效價 31
五、感染乳鼠之病理切片 31
六、牛樟芝-中草藥發酵物影響感染乳鼠之leukocytes 31
七、牛樟芝-中草藥發酵物影響發炎相關細胞激素之表現 32
八、牛樟芝-中草藥發酵物對於以LPS誘導一氧化氮產量之影響 32
第四章 討論 33
壹、牛樟芝-中草藥發酵物對於DENV2不同感染階段之活性 33
貳、牛樟芝-中草藥發酵物對於抗病毒之機制探討 34
參、第二型登革病毒感染C3H/HeN乳鼠模式之探討 34
肆、感染前3天餵食牛樟芝-中草藥發酵物對第二型登革病毒感染C3H/HeN乳鼠之保護效果評估 35
第五章 結論 38
第六章 參考文獻 39
第七章 圖表 47

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