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研究生:陳大隆
研究生(外文):Dalong Chen
論文名稱:植物固醇對非酒精性脂肪肝病人體內血管內皮前驅細胞及血管疾病相關因子之影響
論文名稱(外文):Phytosterols increase circulating endothelial progenitor cells and insulin-like growth factor-1 levels in patients with nonalcoholic fatty liver disease : a randomized crossover study
指導教授:林幸榮林幸榮引用關係
指導教授(外文):Shing-Jong Lin
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:英文
論文頁數:34
中文關鍵詞:植物固醇非酒精性脂肪肝病血管內皮前驅細胞類胰島素生長因子一
外文關鍵詞:Phytosterolsnonalcoholic fatty liver diseaseendothelial progenitor cellinsulin-like growth factor-1
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背景: 植物固醇因為和膽固醇結構相似,可以和膽固醇相互競爭。許多的研究都證實植物固醇有降膽固醇及抗發炎的效果。最近的研究發現脂肪肝病人明顯減少血液中的血管內皮前驅細胞,可能與慢性發炎有關,亦是造成加速血管粥狀硬化的原因。

假說: 植物固醇針對脂肪肝病人血中抗發炎效應而增加血管內皮前驅細胞的數量。

設計: 40個經腹部超音波及問診確定為非酒精性脂肪肝的自願參與者接受試驗。隨機分成兩組各為20人。一組吃植物固醇每天隨餐1.8克4週後休息2週,接著再經過4週的日常飲食。另一組則是先經過4週的日常飲食後休息2週,接著再每天隨餐吃植物固醇1.8克4週。此即所謂的交互試驗。於試驗開始,第4週結束,全部10週試驗結束時各抽一次血液做各項的檢測。其中部分血液是用來定量血中的血管內皮前驅細胞。

納入及排除條件: 25到80歲凡腹部超音波確診為脂肪肝的民眾皆可納入植醇試驗。急性發炎、感染、高心血管風險、心衰竭、慢性腫瘤、內分泌及免疫疾病、懷孕及哺乳者皆排除在外。若有病毒性、自體免疫性肝炎或酒癮者亦排除在外。在試驗開始前,我們亦將服用較可能會干擾實驗的藥或食物的民眾排除,包括降膽固醇如Statins, Ezetamide,Niacin,紅麴等,除油脂如Fibrates,含Omega3多元不飽和脂肪酸的深海魚油等,以及降血糖藥物。至於有服用像Q-10,維生素E等抗氧化劑者則於試驗前2週開始停止服用。試驗中亦請民眾盡量維持原來的生活習慣,包括飲食、運動、生活作息等等。

結果: 平均年齡為52歲。在4週的植物固醇隨餐食用下,可以改善代謝(降低血中低密度膽固醇含量,增加類胰島素成長因子20%,得以改善空腹血糖及糖化血色素)。有抗發炎功效(C反應蛋白降低29%)及抗氧化效果(超氧岐化酶增加10%)。最重要的是血管內皮前驅細胞因而顯著且有意義的增加。不過本試驗中亦發現短期4週的植醇並無法提高一氧化氮的濃度。

結論: 在4週的植物固醇隨餐食用下,可以有意義地改善胰島素抗性,抗發炎,抗氧化並且增加血管內皮前驅細胞的含量。但短期植醇試驗並無助於改善血管內皮功能。

Background: Phytosterols, plant sterols, which have a similar structure to cholesterol, have cholesterol lowering and anti-inflammatory effects. We previously reported that nonalcoholic fatty liver disease (NAFLD) had decreased circulating endothelial progenitor cells (EPCs) number, and this has been suggested as one of the mechanisms behind atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD.

Objective: This study tested the hypothesis that treatment with phytosterols in patients with NAFLD may suppress systemic inflammation and increase circulating EPC levels.

Design: Forty consecutive patients with an abdominal ultrasonographic diagnosis of NAFLD were randomly assigned to phytosterols powder treatment at 1.8g/day for 4 weeks (n=20) or a control group (n=20), with crossover to the alternate therapy for another 4 weeks after 2-week wash-out period. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess circulating EPC levels.

Results: The mean age of the 40 study patients (21 males, 53%) was 51±2 years (range 25-78 years). Four weeks of phytosterols treatment significantly decreased levels of total cholesterol, non high-density lipoprotein cholesterol (non HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting glucose, and hemoglobin A1c (HBA1c), but did not change levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides. Treatment with phytosterols for 4 weeks in patients with NAFLD markedly suppressed high sensitivity C-reactive protein, an inflammatory marker (p=0.0069), and enhanced superoxide dismutase (SOD),an anti-oxidative marker (p=0.0005). We also showed that administration of phytosterols significantly increased the insulin-like growth factor-1 (IGF-1) concentrations (p<0.0001), but failed to have any significant effects on nitric oxide or stromal derived factor-1 levels. Moreover, intake of phytosterols significantly enhanced circulating EPC levels (including: CD34+, CD34+KDR+, CD34+KDR+CD133+, all p<0.05) in NAFLD patients.

Conclusion: Four weeks treatment with phytosterols in NAFLD patients significantly improved insulin resistance, suppressed systemic inflammation, enhanced anti-oxidant capacity, and increased circulating EPC levels. Despite beneficial effect on lipids, glucose and EPCs, short term phytosterols did not seem to improve endothelial function in NAFLD patients.

Trial Registration: clinicaltrials.gov number NCT01875978 completed

English Abstract……………………………………………………………………1-2
Chinese Abstract……………………………………………………………………3-4
List of Abbreviations…………………………………………………………5
Introduction………………………………………………………………………………6-7
Materials and Methods …………………………………………………8-11
Result……………………………………………………………………………………………12-14
Discussion…………………………………………………………………………………15-18
Conclusion…………………………………………………………………………………………19
Perspectives……………………………………………………………………………………20
References…………………………………………………………………………………21-25
Figures and Tables
Figure 1……………………………………………………………………………………26
Figure 2……………………………………………………………………………………27
Figure 3……………………………………………………………………………………28
Figure 4……………………………………………………………………………………29
Table 1………………………………………………………………………………………30
Table 2………………………………………………………………………………………31
Table 3………………………………………………………………………………………32
Appendix………………………………………………………………………………………33-34
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