臺灣博碩士論文加值系統

白血病是因骨髓造血細胞不正常增生並且侵犯骨髓為主的血液惡性疾病，依病程進展包括：急性骨髓性白血病(Acute myeloid leukemia)、急性淋巴性白血病(Acute lymphoblastic leukemia)、慢性骨髓性白血病(Chronic myeloid leukemia)、慢性淋巴性白血病(Chronic lymphocytic leukemia)、多發性骨髓瘤(Multiple myeloma) 以及骨髓增生不良症候群(myelodysplastic syndromes, MDS)。在先前的研究中發現，兒童急性淋巴性白血病（ALL）患者罹患心臟血管疾病的風險是增加的。然而，目前對於白血病患者發生血脂異常的機制尚未完全了解。此外，血液惡性腫瘤的發生，治療和預後可能與脂質、脂蛋白和載脂蛋白的代謝有關。本研究的目的旨在觀察化療前的白血病患者與健康對照組相比，血漿中的脂質、脂蛋白和載脂蛋白的組成與疾病間是否具有相關性。實驗方法則是應用碘克沙醇密度梯度超高速離心從血漿中分離出脂蛋白，再利用生化分析和酵素免疫分析法分別定量脂質和載脂蛋白。研究結果顯示，(i) CML，MDS和MM血漿中的三酸甘油脂（TG）有顯著上升的趨勢，而膽固醇（CHOL）則是下降並有顯著差異，但AML不管是三酸甘油脂（TG）或是膽固醇（CHOL）在統計上均未達到統計意義。(ii) 低密度脂蛋白（LDL）的三酸甘油脂（TG）與膽固醇（CHOL）在AML，MDS和MM的患者中發生改變;其結果顯示，低密度脂蛋白（LDL）含有較多的TG，但較少的膽固醇（CHOL），因而導致TG / CHOL ratio增加。(iii) 三酸甘油脂（TG）在VLDL轉變成LDL過程中發生改變，除了在MDS患者中未達到統計學意義，其他白血病患者AML、CML、MM和CLL皆有顯著下降的趨勢。(iv)與健康對照組相比，所有白血病患者血漿中的高密度脂蛋白膽固醇（HDL）都有顯著下降的表現。(v) 白血病族群與健康對照組比較發現，CML、MDS和CLL 血漿中載脂蛋白AI (apoAI)、載脂蛋白CIII (apoCIII) 與載脂蛋白J (apoJ)的濃度有顯著較低的現象。而載脂蛋白的組間比對結果顯示，AML和MM具有較高濃度表現的載脂蛋白CIII (apoCIII) 與載脂蛋白J(apoJ)。總結，透過研究分析每一種脂質、脂蛋白與載脂蛋白，我們的結果顯示白血病患者脂蛋白代謝可能具有顯著的異常表現。

Leukemia is malignancy of hematological cells. The most common types of leukemia include acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelocytic leukemia (CML), chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS). More ever, multiple myeloma (MM) is a blood cancer related to lymphoma and leukemia. In circulation, lipids are transported through different forms of lipoproteins and imbalance of lipoprotein metabolism might indicate metabolic disorders. In the previous study, childhood ALL survivors were at increased risks of developing late cardiometabolic conditions. However, the lipid profiles in different leukemia types are not fully understood. Moreover, the occurrence, treatment and prognosis of hematological malignancies may be related to the metabolism of lipids and lipoproteins/apolipoproteins. The study aimed to characterize plasma lipid profile and lipoprotein compositions of in patient’s before chemotherapy as compared with healthy volunteers. An iodixanol density-gradient ultracentrifugation was applied to isolate plasma lipoprotein classes from plasma. The lipid contents and apolipoprotein levels were quantified by biochemical assay and ELISA, respectively. The results indicated (i) significant increased TG level and decreased CHOL level was found in CML, MDS and MM, however, no overt alternation of TG and CHOL was found in AML. (ii)The lipid profiles of low-density lipoproteins (LDLs) were altered in patients with AML, MDS and MM. LDL of leukemia patients contained more TG, but less CHOL, resulting in increasing ratio of TG/CHOL ratio. (iii) Moreover, the VLDL-to-LDL ratios of TG were altered in leukemia patients (p 〈0.05), but not reaching statistical significance in MDS. (iv)Especially, the level of plasma high density lipoprotein-cholesterol (HDL) was decreased in all leukemia patients compared with healthy volunteers. (v) CML, MDS and CLL patients had significant low levels of apoAI, apoCIII and apoJ. However, compared with leukemia cohort, AML and MM exhibited high C-III and apoJ. In conclusion, the results suggested the significant abnormalities of lipoprotein metabolism in leukemia patients.

中文摘要 I
Abstract III
致謝 IV
英文延伸摘要 III
表目錄 IX
圖目錄 X
藥品與儀器 XII
簡稱/縮寫 XIV
前言 16
1. 白血病 (Leukemia) 16
1.1 急性骨髓性白血病 (AML) 17
1.2 急性淋巴性白血病 (ALL) 17
1.3 慢性骨髓性白血病(CML) 18
1.4 骨髓增生不良症候群(MDS) 19
1.5 多發性骨髓瘤(MM) 19
1.6 慢性淋巴性白血病(CLL) 20
2. 心血管疾病（Cardiovascular disease, CVD） 20
3. 脂質 (Lipid) 21
3.1 三酸甘油脂 (triglyceride, TG) 21
3.2 膽固醇 (cholesterol, CHOL) 22
4. 脂蛋白 (Lipoprotein) 22
4.1 極低密度脂蛋白 (very low density lipoprotein, VLDL) 22
4.2 低密度脂蛋白 (low-density lipoprotein, LDL) 23
4.3 高密度膽固醇 (high-density lipoprotein cholesterol, HDL-C) 23
5. 載脂蛋白 (Apolipoprotein) 23
5.1 載脂蛋白AI (apoAI) 24
5.2 載脂蛋白B (apoB) 24
5.3 載脂蛋白CIII (apoCIII) 25
5.4 載脂蛋白J (apoJ) 25
實驗目的 26
材料與方法 27
4.1 定量三酸甘油脂 (triglyceride, TG) 28
4.2 定量膽固醇 (cholesterol, CHOL) 29
4.3 定量高密度膽固醇 (high-density lipoprotein cholesterol, HDL-C) 29
5.1. 定量載脂蛋白AI (apoAI) 30
5.2. 定量載脂蛋白B (apoB) 31
5.3. 定量載脂蛋白CIII (apoCIII) 32
5.4. 定量載脂蛋白J (apoJ) 33
5.5 共用試劑配置 35
結果 36
3. 白血病患者脂質與健康者比較結果 37
3.1 白血病患者三酸甘油脂(TG)與健康者比較結果 37
3.2 白血病患者總膽固醇(Total CHOL)與健康者比較結果 37
3.3 白血病患者極低密度脂蛋白(VLDL)中三酸甘油脂(TG)與健康者比較結果… 37
3.4 白血病患者極低密度脂蛋白(VLDL)中膽固醇(CHOL)與健康者比較結果… 37
3.5 白血病患者低密度脂蛋白(LDL)中三酸甘油脂(TG)與健康者比較結果 38
3.6 白血病患者低密度脂蛋白(LDL)中膽固醇(CHOL)與健康者比較結果 38
3.7 白血病患者極低密度脂蛋白(VLDL)中三酸甘油脂(TG)與膽固醇(CHOL)比值(TG/CHOL ratio)與健康者比較結果 38
3.8 白血病患者低密度脂蛋白(LDL)中三酸甘油脂(TG)與膽固醇(CHOL)比值(TG/CHOL ratio)與健康者比較結果 38
3.9 白血病患者極低密度脂蛋白(VLDL)經LPL代謝轉變成低密度脂蛋白(LDL) 後三酸甘油脂(TG)的改變 39
3.10 白血病患者極低密度脂蛋白(VLDL)經LPL代謝轉變成低密度脂蛋白(LDL) 後膽固醇(CHOL)的改變 39
3.11 白血病患者高密度脂蛋白(HDL)與健康者比較結果 39
3.12 白血病患者載脂蛋白AI (apoAI)與健康者比較結果 39
3.13 白血病患者載脂蛋白B (apoB)與健康者比較結果 40
3.14 白血病患者載脂蛋白CIII (apoCIII)與健康者比較結果 40
3.15 白血病患者載脂蛋白J (apoJ)與健康者比較結果 40
4. 白血病族群脂質、脂蛋白與載脂蛋白組間比較結果 41
4.1 白血病族群三酸甘油脂(TG)組間比較 41
4.2 白血病族群總膽固醇(Total CHOL)組間比較 41
4.3 白血病族群極低密度脂蛋白(VLDL)中三酸甘油脂(TG)組間比較 41
4.4 白血病族群極低密度脂蛋白(VLDL)中膽固醇(CHOL)組間比較 41
4.5 白血病族群低密度脂蛋白(LDL)中三酸甘油脂(TG)組間比較 42
4.6 白血病族群低密度脂蛋白(LDL)中膽固醇(CHOL)組間比較 42
4.7 白血病族群極低密度脂蛋白(VLDL)中三酸甘油脂(TG)與膽固醇(CHOL)比值(TG/CHOL ratio)組間比較 42
4.8 白血病族群低密度脂蛋白(LDL)中三酸甘油脂(TG)與膽固醇(CHOL)比值(TG/CHOL ratio)組間比較 42
4.9 白血族群者極低密度脂蛋白(VLDL)經LPL代謝轉變成低密度脂蛋白(LDL) 後三酸甘油脂(TG)的改變組間比較 43
4.10 白血病族群極低密度脂蛋白(VLDL)經LPL代謝轉變成低密度脂蛋白(LDL) 後膽固醇(CHOL)的改變組間比較 43
4.11 白血病族群高密度脂蛋白(HDL)組間比較 43
4.12 白血病族群載脂蛋白AI (apoAI)組間比較 43
4.13 白血病族群載脂蛋白B (apoB)組間比較 44
4.14 白血病族群載脂蛋白CIII (apoCIII)組間比較 44
4.15 白血病族群載脂蛋白J (apoJ)組間比較 44
討論 45
結論 50
參考文獻 51

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