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研究生: 謝愷和
Hsieh, Kai-Ho
論文名稱: 微膠細胞之自噬作用在腦部缺血/再灌流壓力下對型態轉換之作用
Autophagy mediates phenotypic transition of microglia under brain ischemia/reperfusion
指導教授: 張雅雯
Chang, Ya-Wen
學位類別: 碩士
Master
系所名稱: 醫學院 - 生理學研究所
Department of Physiology
論文出版年: 2024
畢業學年度: 112
語文別: 中文
論文頁數: 127
中文關鍵詞: 缺血/再灌流微膠細胞型態轉換自噬作用發炎反應
外文關鍵詞: Ischemia/reperfusion, microglia, phenotypic transition, autophagy, inflammation
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  • 中文摘要 I 英文摘要 III 致謝 (Acknowledgement) VI 目錄與圖表目錄 IX 縮寫 (Abbreviations) XII 第一章、 緒論 (Introduction) 1 一、 腦中風 (Stroke) 1 二、 缺血性腦中風之致病機轉 2 三、 微膠細胞 (Microglia) 在缺血性腦中風之參與 5 四、 研究假說 11 第二章、 材料與方法 (Materials and Methods) 13 一、 藥品與試劑 13 二、 細胞培養 14 三、 體外微膠細胞缺血/再灌流模式之建立 15 四、 細胞加藥處理 16 五、 基因敲除 (Genetic knockdown) 17 六、 蛋白質萃取及濃度測定 18 七、 西方墨點法 (Western blotting) 19 八、 核醣核酸 (Ribonucleic acid; RNA) 萃取及濃度測定 22 九、 即時定量聚合酶連鎖反應 (Real-time Quantitative Polymerase Chain Reaction; RT-qPCR) 23 十、 統計分析 24 第三章、 結果 (Results) 25 一、 缺血/再灌流對BV-2與CHME-3微膠細胞活化之調控 25 二、 缺血/再灌流對BV-2與CHME-3微膠細胞中M1/M2型態標記物之調控 25 三、 不同缺血時長對BV-2與CHME-3微膠細胞極化現象之調控 27 四、 缺血/再灌流對BV-2與CHME-3微膠細胞中自噬作用之調控 29 五、 自噬作用促進劑與抑制劑對缺血/再灌流處理之BV-2與CHME-3微膠細胞中自噬作用之調控 30 六、 atg5基因敲除對BV-2與CHME-3微膠細胞中自噬作用活性之調控 33 七、 atg5基因敲除對缺血/再灌流處理之BV-2與CHME-3微膠細胞中自噬作用之調控 34 八、 atg5基因敲除後所減少之自噬作用活性對缺血/再灌流處理之BV-2與CHME-3微膠細胞中M1/M2型態轉換之調控 36 九、 缺血/再灌流對BV-2與CHME-3微膠細胞中NR4A1以及NF-κB表現量之調控 37 十、 結論 38 第四章、 討論 (Discussion) 40 一、 M1/M2型微膠細胞之探討對於治療缺血性腦中風之潛力 40 二、 微膠細胞株之選用對於缺血性腦中風研究之影響 40 三、 M1型微膠細胞在缺血性腦中風當中所扮演的角色 41 四、 轉錄與轉譯上之修飾對於缺血/再灌流下M1/M2標記物之影響 42 五、 M0、M1與M2型態微膠細胞之間轉換的模式可能有助於探討各階段之缺血性腦中風之可能治療手段 43 六、 自噬作用之降解過程可能對於M1/M2微膠細胞之轉換是重要的關鍵之一 44 七、 細胞培養環境中之差異可能導致自噬作用藥劑產生不同之藥理效果 45 八、 自噬作用於調控M1/M2型微膠細胞轉換之可能分子機制之探討 47 九、 總結 48 第五章、 未來展望 (Future works) 50 第六章、 參考文獻 (References) 51 第七章、 結果圖與表 (Figures and Tables) 57

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