臺灣博碩士論文加值系統

幽門螺旋桿菌感染宿主後，容易導致胃炎、胃潰瘍與胃癌等疾病。台灣擁有豐富的藻類資源，其中褐藻萃取物經過許多文獻指出具有廣泛的生理活性，因此本報告旨在觀察半葉馬尾藻萃取物對幽門螺旋桿菌感染宿主是否能產生影響。將半葉馬尾藻分別以熱水和絕對酒精萃取後，得到產率13.5% 之半葉馬尾藻水萃物 (Sargassum hemiphyllum water extract , SHw) 和產率2.1% 的半葉馬尾藻酒萃物 (Sargassum hemiphyllum ethanol extract , SHe)。以RAW264.7測定萃取物的抗發炎能力，結果顯示兩者都有良好的抗發炎活性；從AGS (Human caucasian gastric adenocarcinoma) 細胞模式來看，降低幽門螺旋桿菌黏附細胞可以減少幽門螺旋桿菌感染率，SHw在Post-treatment有較佳的效果，而SHe則是於Co-treatment發揮作用，兩種萃取物促使幽門螺旋桿菌的感染率下降約40%，另經分析後可知SHw和SHe能夠抑制幽門螺旋桿菌黏附素babA與alpA。最後以動物實驗來驗證細胞實驗之結果，SHe和SHw在Post-treatment能顯著減少小鼠胃中的幽門螺旋桿菌菌數，且餵食半葉馬尾藻萃取物能減緩細胞浸潤並降低IL-6、TNF-α之含量。綜合上述，半葉馬尾藻萃取物能夠降低幽門螺旋桿菌感染，調降幽門螺旋桿菌引起的發炎反應，達到保護宿主之功效，在未來應用上具備天然藥物開發潛力。

After infected by Helicobacter pylori, the pathogen may cause deseases, such as gastritis, gastric ulcer, and gastric cancer. Taiwan has rich algae resources, among which the brown algae extracts have been shown to possess board biological activities. Here, we aim to study whether the Sargassum hemiphyllum extracts have preventive effects on the Helicobacter pylori infection. The Sargassum hemiphyllum were extracted with hot water (SHw) and absolute alcohol (SHe), respectively. The yields were 13.5% and 2.1% by water extraction and by ethanol extraction, respectively. RAW264.7 was used to determine the anti-inflammatory effects of the extract. The results showed that both extracts have anti-inflammatory activity. On the AGS cell (Human caucasian gastric adenocarcinoma) experiments, decreasing the H. pylori to adhere cells could reduce the H. pylori infection. SHw and SHe had an improved effect on infection rate that caused by H. pylori infection under Post-treatment and Co-treatment, respectively. Both extracts inhibit the infection rate of Helicobacter pylori about 40%. Moreover, SHw and SHe can inhibit the H. pylori adhesin babA and alpA. In the infected BALB/c model, SHw and SHe significantly reduced the number of H. pylori in the stomach of mice in Post-treatment, and the feeding of Sargassum hemiphyllum extracts could slow down the infiltration of cells and reduced IL-6 and TNF- alpha expression. In summary, the Sargassum hemiphyllum extracts can inhibit H. pylori infection, reduce the inflammatory response, and protect the host from infection of H. pylori. Sargassum hemiphyllum extracts have a high potentially in many applications, in particular the drug development.

目錄 III
圖目錄 VII
表目錄 IX
前言 1
第一章、文獻回顧 2
1. 幽門螺旋桿菌 2
1-1. 幽門螺旋桿菌簡介 2
1-2. 幽門螺旋桿菌致病因子 3
1-2-1. 鞭毛 (Flagella) 3
1-2-2. 尿素酶 (Urease) 3
1-2-3. 細胞毒素相關基因 (Cag PAI & CagA) 3
1-2-4. 空泡性細胞毒素 (Vacuolating toxin, Vac A) 4
1-2-5. 黏附素 (Adhesin) 4
1-3. 慢性發炎 (Chronic inflammation) 4
1-4. 流行病學調查 5
1-5. 幽門螺旋桿菌感染之機制與致癌之風險 5
1-6. 幽門螺旋桿菌之治療 6
2. 半葉馬尾藻 (Sargassum hemiphyllum) 7
2-1. 海藻 (Seaweed) 之簡介 7
2-2. 褐藻 (Brown seaweed) 8
2-3. 半葉馬尾藻 8
2-4. 褐藻醣膠 (Fucoidan) 8
2-5. 褐藻素 (Fucoxanthin) 9
2-6. 海藻多酚 (Phlorotannins) 9
3. 研究目的 11
第二章、實驗設計流程 12
1. 半葉馬尾藻萃取物分析並結合細胞模式觀察抑菌能力 12
2. 半葉馬尾藻萃取物對於幽門螺旋桿菌感染小鼠之保護效果 13
第三章、材料與方法 14
1.材料 14
1-1. 樣品原料與萃取溶劑 14
1-2. 抗氧化試驗 14
1-3. 成分分析 14
1-4. 菌株及細胞株 14
1-5. 培養基 14
1-5-1. 細菌培養基 14
1-5-2. 細胞培養基 15
1-6. 幽門螺旋桿菌培養 15
1-7. 細胞存活率試劑 15
1-8. 實驗動物 15
1-9. RNA萃取套組 15
1-10. 反轉錄反應試劑 15
1-11. 即時定量聚合酶連鎖反應試劑 16
1-12. 組織切片 16
1-13. 組織染色 16
1-13-1. H&E stain 16
1-13-2. Giemsa stain 16
2. 儀器設備 16
3. 實驗方法 17
3-1. 實驗樣品製備 17
3-1-1. 半葉馬尾藻熱水萃取法 17
3-1-2. 半葉馬尾藻乙醇萃取法 17
3-2. 半葉馬尾藻特性分析 17
3-2-1. 膠體滲透層析 (Gel permeation chromatography, GPC) 17
3-2-2. 高效能液相層析 (High performance liquid chromatography, HPLC) 17
3-2-3. 總酚含量測定 18
3-2-4. 硫酸根含量測定 18
3-2-5. 抗氧化能力測定 18
3-3. 幽門螺旋桿菌培養及鑑定 19
3-3-1. 培養基之製備 19
3-3-2. 幽門螺旋桿菌培養與保存 19
3-3-3. 幽門螺旋桿菌之鑑定 19
3-3-4. 尿素酶活性試驗 20
3-3-5. 幽門螺旋桿菌之計數 20
3-3-6. 幽門螺旋桿菌之PCR測定 20
3-3-7. 半葉馬尾藻抑制尿素酶活性分析 21
3-3-8. 半葉馬尾藻抑菌能力分析 21
3-4. 細胞實驗 22
3-4-1. 細胞培養 22
3-4-2. 細胞之保存 22
3-4-3. 細胞之活化 22
3-4-4. 細胞毒性試驗 22
3-4-5. 一氧化氮生成分析 (NO assay) 23
3-4-6. 幽門螺旋桿菌對於AGS細胞之感染比測試 23
3-4-7. 幽門螺旋桿菌貼附細胞能力測試 23
3-4-8. 偵測細胞內細菌與細胞因子RNA表現量 23
(1)抽取細胞之Total RNA 24
(2)反轉錄反應 (Reverse transcription, RT) 24
(3)即時聚合酶連鎖反應 (Real-time polymerase chain reaction, RT-PCR) 24
3-5-1. 實驗小鼠 25
3-5-2. 幽門螺旋桿菌感染模式 25
3-5-3. 尿素酶活性試驗 25
3-5-4. 幽門螺旋桿菌分離培養 25
3-5-5. 偵測胃組織中細菌與細胞因子RNA表現量 26
(1)抽取胃組織之Total RNA 26
(2)反轉錄反應 (Reverse transcription, RT) 26
(3)即時聚合酶連鎖反應 (Real-time polymerase chain reaction, RT-PCR) 26
3-5-6. 石蠟切片 27
3-6. 組織染色 27
3-6-1. H&E stain 27
3-6-2. Giemsa stain 27
3-7. 血液分析 28
3-8. 統計分析 28
第四章、結果 29
1. 半葉馬尾藻化學特性與生物活性分析 29
2. 半葉馬尾藻對於幽門螺旋桿菌感染之細胞模式 29
2-1. 幽門螺旋桿菌的培養與鑑定 29
2-2. 半葉馬尾藻對於幽門螺旋桿菌之活性影響 29
2-3. 半葉馬尾藻對幽門螺旋桿菌之抑制能力 30
2-4. 半葉馬尾藻抗發炎能力分析 30
2-5. 半葉馬尾藻降低幽門螺旋桿菌之黏附能力 30
2-6. 半葉馬尾藻降低幽門螺旋桿菌感染之活性與機制 31
3. 半葉馬尾藻對於幽門螺旋桿菌感染之動物模式 31
3-1. 幽門螺旋桿菌感染BALB/c小鼠動物模式建立 31
3-2. 半葉馬尾藻降低幽門螺旋桿菌在BALB/c小鼠中之菌量 31
3-3. 探討半葉馬尾藻萃取物於幽門螺旋桿菌感染小鼠中的免疫調節能力 32
第五章、討論 34
1. 半葉馬尾藻萃取物成分與生理活性 34
2. 半葉馬尾藻抑制幽門螺旋桿菌之生長 35
3. 半葉馬尾藻對於LPS誘導RAW264.7產生NO量之影響 35
4. 半葉馬尾藻抑制幽門螺旋桿菌感染細胞 36
5. 半葉馬尾藻於動物模式下降低幽門螺旋桿菌感染與發炎反應 38
第六章、結論 41
第七章、參考文獻 42
第八章、圖 53
第九章、表 79

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