| 研究生: |
陳蕾 Chan, Loi |
|---|---|
| 論文名稱: |
發展以載脂蛋白為基礎的診斷平台之轉譯醫學應用 An apolipoprotein-based diagnostic platform for translational medicine applications |
| 指導教授: |
楊孔嘉
Young, Kung-Chia |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 醫學檢驗生物技術學系 Department of Medical Laboratory Science and Biotechnology |
| 論文出版年: | 2018 |
| 畢業學年度: | 106 |
| 語文別: | 中文 |
| 論文頁數: | 92 |
| 中文關鍵詞: | 脂蛋白 、載脂蛋白 、肝臟疾病 、酵素結合免疫吸附分析法 、基於載脂蛋白的診斷平台 |
| 外文關鍵詞: | lipoprotein, apolipoprotein, liver diseases, ELISA, apolipoprotein-based diagnostic platform |
| 相關次數: | 點閱:90 下載:2 |
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在人體中,脂質會通過不同形式的脂蛋白進行轉運,其中脂蛋白代謝的失衡會導致代謝紊亂,如冠狀動脈疾病,動脈粥樣硬化和非酒精性肝病。脂蛋白也是受體介導的外源性疏水藥物化合物以及某些病原體的攝取途徑,如丙型肝炎病毒和黃病毒科家族成員。人類的脂蛋白根據其大小和密度進行分類。低密度脂蛋白,包括極低密度脂蛋白 (VLDL),中密度脂蛋白 (IDL) 和低密度脂蛋白 (LDL),均含apoB-100,並具有致動脈粥樣硬化脂蛋白的特徵; 另外,高密度脂蛋白 (HDL) 主要含有apoAI,被認為是抗動脈粥樣硬化脂蛋白。血漿中的脂蛋白顆粒是由 >60種相關的載脂蛋白 (apolipoprotein, apo) 所組成,致動脈粥樣硬化脂蛋白中的脂載量以及載脂蛋白的量與代謝紊亂的風險高度相關。本研究的目的是開發一種診斷平台,用於量化整體與單個脂蛋白分子中的脂質和脂質含量。初步選擇載脂蛋白AI (apoAI),載脂蛋白B (apoB),載脂蛋白CIII (apoCIII) 和載脂蛋白J (apoJ) 進行檢測,原因為1) 載脂蛋白B和載脂蛋白AI分別在低密度脂蛋白和高密度脂蛋白中佔優勢;2) 載脂蛋白CIII是脂蛋白代謝的關鍵調節蛋白;3)載脂蛋白J與細胞內脂質代謝事宜有關。通過調整緩衝系統並優化針對不同類型載脂蛋白的抗體,可以捕獲脂蛋白而不破壞它們的結構; 於是,定量相關分析基於載脂蛋白的診斷平台的信號於每個測試的單個載脂蛋白之不同方法。此外,基於載脂蛋白的診斷平台用於評估不同疾病患者 (包括肝癌,非酒精性脂肪肝病/非酒精性脂肪性肝炎,病毒性肝炎) 患者的載脂蛋白含量。
In human, lipids are transported through different forms of lipoproteins, and imbalance of lipoprotein metabolism induces metabolic disorders, such as coronary artery disease, atherosclerosis, and nonalcoholic liver diseases. Lipoproteins also are receptor-mediated uptake routes for exogenous hydrophobic pharmaceutical compounds as well as certain pathogens, such as hepatitis C virus and other members in the flaviviridae family. Human lipoproteins are classified according to their sizes and densities. Low-density lipoproteins, including very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) are apoB-100-containing and characterized as proatherogenic lipoproteins. Meanwhile, high density lipoprotein (HDL) contains predominantly apoAI and is considered as an anti-atherogenic lipoprotein. Plasma lipoprotein particles are composed of a smorgasbord of >60 kinds of associated apolipoproteins (apos). Moreover, the lipid loading capacities as well as the quantities of apos in proatherogenic lipoproteins associate highly with the risk of metabolic disorders. The aim of this study is to develop a diagnostic platform for quantification of apos and lipid content in intact lipoprotein particles. ApoAI, apoB, apoCIII, and apoJ were selected for testing due to the facts that 1) apoB and apoAI are predominant in low- and high-density lipoproteins, respectively; 2) apoCIII is one of the key regulators of lipoprotein metabolism; 3) apoJ is associated with intracellular metabolism events. By adjusting the buffer system and optimizing the antibodies against apos, the lipoproteins were captured without disrupting their structure. The correlations were evaluated of various tests with the apo-based diagnostic platform which quantified only single apo per particle. Furthermore, the apo-based diagnostic platform was translationally applied to evaluate the quantities of apos in patients with different diseases, including liver cancer, nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis and viral hepatitis.
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校內:2023-12-31公開