臺灣博碩士論文加值系統

A 型流感病毒 (Influenza A virus) 會使呼吸道上皮細胞壞死、脫落，造成呼吸道的自然防禦受損，而持續釋放的細胞激素會加劇發炎反應，對於高危險群患者易造成繼發性感染，例如肺炎，甚至引發熱休克或多重器官衰竭，因此造成導致病患死亡，因此需要研究有效的物質來抑制流感病毒的感染。薑黃素 (Curcumin) 和槲皮素 (Quercetin) 已被證實有許多生理活性，但難溶於水中使得生物利用性差，而作為碳奈米材料的新成員碳量子點 (Carbon quantum dots) 容易接上官能基，使其具有更好的生物相容性和更低的毒性。因此本研究將探討薑黃素、槲皮素及其碳量子點對於A型流感病毒 (A/WSN/33) 感染之保護效果，細胞實驗使用犬腎細胞進行病毒斑試驗，結果顯示在共同處理時10 µg/mL薑黃素和槲皮素碳量子點的病毒斑抑制率分別為51.11%和94.79%，接著以2x104 PFU/mL的病毒液以噴霧方式感染小鼠，並以鍛燒於180℃ 的薑黃素和270℃ 的槲皮素碳量子點以治療 (Post-treatment)、預防 (Per-treatment) 和共培養 (Co-treatment) 的方式給予6週齡 BALB/c 小鼠，結果顯示預防組的180℃ 的薑黃素碳量子點和治療組270℃ 的槲皮素碳量子點能改善小鼠存活率達83.3%，且經組織切片結果顯示能顯著降低細胞浸潤及支氣管上皮增厚情形，而薑黃素碳量子點能顯著增加肺組織中的IL-10以降低肺部的炎症反應，以上結果證明薑黃素和槲皮素碳量子點對感染流感病毒的小鼠具有保護的效果。

Influenza A virus can cause necrosis and shedding of respiratory epithelium, which can damage the natural defense of the respiratory tract. The sustained release of cytokines can aggravate the inflammatory response. For high-risk groups, it is easy to cause secondary infections, such as pneumonia, and even cause heat shock. Or multiple organ failure, resulting in the death of the patient, so it is necessary to study effective substances to inhibit the infection of influenza virus. Curcumin and quercetin have been shown to have many physiological activities, but poorly soluble in water makes bioavailability poor, and Carbon quantum dots, a new member of carbon nanomaterials, are easily attached to functional groups, making them better bio-phases. Capacitive and lower toxicity. Therefore, this study will investigate the protective effect of Curcumin, quercetin and its carbon quantum dots on influenza A virus (A/WSN/33) infection. In vitro using MDCK cell for plaque assays, the results show that when co-treatment The plaque inhibition rates of 10 μg/mL Curcumin and quercetin carbon quantum dots were 51.11% and 94.79%, respectively, followed by aerosol inhalation infection of the mice with 2x104 PFU/mL of virus. Curcumin carbon quantum dots at 180 °C and quercetin carbon quantum dots at 270 °C were administered to 6-week-old BALB/c mice in the form of Post-treatment, Pre-treatment, and Co-treatment, and the results showed that the Curcumin carbon quantum dots at 180 °C in the pre-treatment and quercetin carbon quantum dots at 270 °C in post-treatment can improve the survival rate of mice by 83.3%, and the results of histopathology analysis can significantly reduce cell infiltration and respiratory bronchiole epithelial thickening, while curcumin carbon quantum dots significantly increased IL-10 in lung tissue to reduce inflammation in the lungs. The above results demonstrate Curcumin and quercetin carbon quantum dots can protective effect on mice infected with influenza virus.

壹、 前言..............................1
貳、 文獻回顧..........................2
一、 流感病毒 .........................2
1. 流感病毒起源......................2
2. 流感病毒之流行病學.................2
3. 流感病毒分類與命名.................2
4. 流感病毒結構......................3
5. 流感病毒的複製週期.................3
6. 流感病毒致病機制...................4
7. 流感病毒變異......................4
8. 流感病毒的傳播與症狀...............5
9. 流感病毒感染後的免疫反應............5
10. 流感病毒之預防與治療...............6
二、 多酚 (Polyphenol).................6
1. 類黃酮 (Flavonoid)................7
2. 槲皮素 (Quercetin)................7
3. 薑黃素 (Curcumin).................9
三、 碳奈米材料.......................10
1. 碳量子點 (Carbon quantum dots, CQD)..11
2. 碳量子點的合成...................11
3. 碳量子點的表面修飾................11
4. 碳量子點的應用....................12
參、 實驗設計流.......................13
一、 樣品製備及成分分析................13
二、 細胞實驗 (In vitro)..............13
三、 動物實驗 (In vivo)...............13
肆、 實驗材料與方法...................14
一、 實驗材料.........................14
1. 樣品.............................14
2. 抗氧化能力試驗....................14
3. 病毒株...........................14
4. 細胞株...........................14
5. 細胞培養相關試劑..................14
6. 實驗動物.........................15
7. 酵素結合免疫吸附分析法 (Enzyme-linked immunosorbent assay, ELISA)............................15
8. RNA萃取套組.......................16
9. 反轉錄反映試劑.....................16
10. 即時定量聚合酶鏈鎖反應試劑..........16
11. 組織切片 ..........................17
二、 儀器設備 ..........................17
三、 實驗方法...........................17
1. 實驗樣品製備........................17
2. 成分分析............................18
3. 流感病毒增殖培養 (Influenza virus amplify)...20
4. 細胞實驗 (In vitro).................20
5. 動物實驗 (In vivo)..................23
6. 統計分析 (Statistics analysis)......26
伍、 結果................................27
一、 薑黃素及槲皮素碳量子點之成分分析及特性分析...27
1. 薑黃素及槲皮素碳量子點之抗氧化能力.....27
2. 薑黃素及槲皮素碳量子點之元素分析.......27
3. 以穿透式電子顯微鏡觀察薑黃素及槲皮素碳量子點之外觀...27
二、 薑黃素及槲皮素碳量子點抗H1N1感染之細胞模式評估......29
1. 薑黃素及槲皮素碳量子點對MDCK細胞之細胞毒性.........29
2. 薑黃素及槲皮素碳量子點抑制H1N1之病毒斑生成.........29
3. 薑黃素及槲皮素碳量子點對LPS誘導之發炎反應效果評估...29
三、 薑黃素及槲皮素碳量子點抗H1N1感染之動物模式評估......30
1. 動物外觀及行為模式評估動物發病情形.................30
2. 薑黃素及槲皮素碳量子點對感染H1N1小鼠發病情形與存活率之影響......................................................30
3. 薑黃素及槲皮素碳量子點對感染H1N1小鼠血液分析.......31
4. 薑黃素及槲皮素碳量子點對感染H1N1小鼠肺損傷情形.....31
5. 薑黃素及槲皮素碳量子點對感染H1N1小鼠血液中細胞激素抗原表現.....................................................32
6. 薑黃素及槲皮素碳量子點對感染H1N1小鼠支氣管沖提液中細胞激素抗原表現...............................................32
7. 薑黃素及槲皮素碳量子點對感染H1N1小鼠肺組織中A/WSN/33之HA基因表現..............................................32
8. 薑黃素及槲皮素碳量子點對感染H1N1小鼠肺組織中細胞激素基因表現....................................................33
陸、 討論............................................34
一、 薑黃素及槲皮素碳量子點之成分分析及特性分析.........34
二、 薑黃素及槲皮素碳量子點之抗H1N1之細胞模式評估.......35
三、 薑黃素及槲皮素碳量子點之抗H1N1之動物模式評估.......37
1. A型流感病毒噴霧感染動物模式.......................37
2. 薑黃素及槲皮素碳量子點對感染H1N1小鼠肺損傷情形.....37
柒、 結論............................................40
捌、 參考資料.........................................41
玖、 圖表............................................50

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