臺灣博碩士論文加值系統

輔酶Q10 (Coenzyme Q10, CoQ10)的還原態—Ubiquinol (QH2)在週邊循環中，可當作抗氧化物質，與自由基作用變成氧化態(Ubiquinone, Q)。輔酶Q10 也參與維生素E 的再生、預防脂質過氧化。本實驗以高膽固醇血症患者為受試者，探討在長期合併攝取紅麴製品，是否影響血漿中輔酶Q10的濃度，並探討調節血脂之功效和可能機制；另外探討紅麴製品合併輔酶Q10，預防脂質氧化的功效。
實驗係以紅麴製品，給予高膽固醇血症者(24 人)連續攝取紅麴錠劑四個月(一天四顆，每顆含5 毫克monacolin K)，每個月抽取血液評估其對血脂質、本體脂蛋白B 及抗氧化功能—輔酶Q10、維生素E、脂質過氧化物TBARS(Thiobarbituric acid reactive substances)；另外招募高膽固醇血症者(37 人)，分成三組，分別為紅麴組(M) (monacolins 12 毫克)、輔酶Q10 紅麴組(MQ)(monacolins 12 毫克加 CoQ10 30 毫克)及輔酶Q10 紅麴高劑量組(HMQ) (monacolins 24 毫克加CoQ10 60 毫克)，參與調整期(2週)、實驗期(6週)及排空期(2週)三階段試驗。抽血檢驗分析膽固醇、血脂質與LDL-延遲反應(LDL lag time)。數據以mean ± SEM 表示，以Student’s t test 進行統計分析，當 p<0.05 代表有統計上的差異。
結果顯示，攝取紅麴製品4 個月後攝食前相比，其血清總膽固醇、低密度脂蛋白膽固醇、本體脂蛋白B 的濃度皆顯著下降，而高密度脂蛋白膽固醇濃度、血漿維生素E 濃度則無顯著差異；食用紅麴製品1 個月後與攝食前相比，其輔酶Q10 之濃度顯著下降。受試者在合併補充紅麴製品六週後，其血漿中MDA 濃度顯著下降，且LDL 氧化時間顯著延長，而添加輔酶Q10 的組別於排空期後，LDL 氧化延遲時間仍維持在其範圍中。
長期攝取紅麴製品，會藉由抑制HMG CoA reductase 活性與降低本體脂蛋白B 濃度，而降低血清總膽固醇與低密度脂蛋白膽固醇的濃度，同時MDA 濃度顯著降低；合併給予輔酶Q10 可延緩低密度脂蛋白之氧化，有助降低動脈粥狀硬化之發生或進展。

Recent studies showed a possibly interruption of monacolins, active compounds of Monascus rice powder, on coenzyme Q10 biosynthesis. Since the benefits of cholesterol-lowing effect on Monascus rice powder has been
revealed, the utilization of coenzyme Q10 still remains controversial. Thus, a clinical trial was conducted to investigate lipid-lowering and antioxidative effects of combined red yeast rice extract and coenzyme Q10 (CoQ10)
supplementation on hypercholesterolemic subjects.
24 subjects were recruited and supplemented by Monascus products for 4 months, which contained monacolin K 20mg. Blood samples were collected every months for lipids, apolipoprotein B, coenzyme Q10 and α-tocopherol determination. Forty subjects were recruited and were randomly divided into three groups such as Monascus rice powder 500 mg (M), equivalent to monacolins 12 mg; Monascus rice powder 500 mg plus CoQ10 30 mg (MQ), and Monascus rice powder 1 g plus CoQ10 60 mg (HMQ) by different doses supplementation. The supplementations administrated for 6 weeks, blood samples were collected every two weeks for cholesterol and low density lipoprotein (LDL) lag time, and TBARS(Thiobarbituric acid reactive substances) determination.
Results showed that the subjects had lower serum total cholesterol, LDL cholesterol, and apolipoprotein B concentration after four months of supplementation. Moreover, there were no alterations on high density lipoprotein (HDL) cholesterol level and α-tocopherol level. After one months supplementation, the concentration of plasma coenzyme Q10 significant decreased. In LDL-lag time, the data displayed a significant slower production
of conjugated dienes in all groups after six weeks of supplementation. However, in CoQ10 supplementing groups, the effect sustained after ceasing supplementation for two weeks. The concentration of plasma MDA level significant decreased in all groups after six weeks of supplementation.
The results confirmed the lipid-lowering effects of monacolins by inhibiting Hydroxymethyl glutaryl CoA reductase (HMG CoA reductase) activity and decreasing the concentration serum apolipoprotein B. Furthermore, addition of at least 30 mg CoQ10 could significantly enhance LDL antioxidative capacity in hypercholesterolemic subjects.

中文摘要 ...................................................................................................................... i
英文摘要 .................................................................................................................... iii
致 謝 ..................................................................................................................... v
目 錄 .................................................................................................................... vii
圖目錄 ......................................................................................................................x
表目錄 ..................................................................................................................... xi
第一章、 緒 論 .......................................................................................................... 1
第二章、 文獻回顧 ...................................................................................................... 2
第一節、 高膽固醇血症 .................................................................................................. 2
一、 高膽固醇血症之盛行率 ...................................................................................... 2
二、 高膽固醇血症之生活型態的調整 ...................................................................... 2
三、 高膽固醇血症之藥物控制 .................................................................................. 3
四、 高膽固醇血症之飲食控制 .................................................................................. 3
五、 高膽固醇血症患者之膽固醇代謝 ...................................................................... 4
第二節、 紅麴 ......................................................................................................... 6
一、 紅麴簡介 .............................................................................................................. 6
二、 紅麴之活性成分及內生性膽固醇代謝 .............................................................. 6
第三節、 輔酶Q10 (Coenzyme Q10) .......................................................................... 8
一、 輔酶Q10 的代謝與生合成途徑 ........................................................................... 8
二、 輔酶Q10 與抗氧化功能 ....................................................................................... 9
三、 輔酶Q10 與粒線體功能 ..................................................................................... 10
第四節、 輔酶Q10 與紅麴的交互作用 ................................................................... 11
第三章、 實驗材料與方法 ......................................................................................... 12
第一節、 受試者招募與篩檢 ........................................................................................ 12
第二節、 實驗一：長期補充紅麴產品試驗 ................................................................ 13
一、 實驗設計 ............................................................................................................ 13
二、 樣本收集及處理 ................................................................................................ 14
三、 統計分析 ............................................................................................................ 25
viii
第三節、 實驗二：合併投予紅麴及輔酶Q10 產品試驗 ............................................. 26
一、 實驗設計 ............................................................................................................ 26
二、 樣本收集及處理 ................................................................................................ 26
三、 統計分析 ............................................................................................................ 29
第四章、 結 果 ........................................................................................................ 30
第一節、 實驗一：長期補充紅麴產品試驗 ................................................................ 30
一、 受試者之體位測量 ............................................................................................ 30
二、 受試者飲食紀錄 ................................................................................................ 30
三、 受試者對於紅麴製品之順應性（Compliance） ............................................. 30
四、 脂質代謝 ............................................................................................................ 31
(1) 血清總膽固醇、低密度脂蛋白膽固醇、本體脂蛋白B 濃度 ..................... 31
(2) 血清三酸甘油酯、高密度脂蛋白膽固醇濃度 ............................................. 32
五、 紅血球之脂肪酸組成 ........................................................................................ 32
六、 抗氧化功能 ........................................................................................................ 32
(1) 血漿輔酶Q10 濃度 .......................................................................................... 32
(2) 血漿及紅血球維生素E 濃度 ......................................................................... 33
(3) 血漿MDA 濃度 ............................................................................................... 33
七、 肝腎功能指標及其他生化分析 ........................................................................ 33
(1) 肝腎功能 ......................................................................................................... 33
(2) 心肌功能 ......................................................................................................... 33
第二節、 實驗二：合併投予紅麴及輔酶Q10 產品試驗 ............................................. 34
一、 受試者基本資料、體位測量 ............................................................................ 34
二、 受試者飲食紀錄 ................................................................................................ 34
三、 受試者對於紅麴製品之順應性（Compliance） ............................................. 34
四、 脂質代謝 ............................................................................................................ 35
(1) 血清總膽固醇、低密度脂蛋白膽固醇濃度 ................................................. 35
(2) 血清三酸甘油酯、高密度脂蛋白膽固醇濃度 ............................................. 35
五、 抗氧化功能 ........................................................................................................ 36
(1) 血漿MDA 濃度 ............................................................................................... 36
ix
(2) LDL 氧化延遲時間 ......................................................................................... 36
六、 肝腎功能指標 .................................................................................................... 36
第五章、 討 論 ......................................................................................................... 37
第一節、 長期攝取紅麴製品對於血脂質代謝之影響 ................................................ 37
一、 紅麴製品與血膽固醇 ........................................................................................ 37
二、 紅麴製品與血清本體脂蛋白B ......................................................................... 39
(1) 紅麴製品降低本體脂蛋白B 之生成與異化作用 ......................................... 39
(2) 紅麴製品降低本體脂蛋白B 之分泌 ............................................................. 40
(3) 本體脂蛋白B 與血清總膽固醇、低密度脂蛋白膽固醇濃度之相關性探討 .
......................................................................................................................... 41
三、 紅麴製品與三酸甘油酯及高密度脂蛋白膽固醇濃度 .................................... 43
(1) 紅麴製品對於三酸甘油酯濃度之影響 ......................................................... 43
(2) 紅麴製品對於高密度脂蛋白膽固醇濃度之影響 ......................................... 44
第二節、 紅麴製品與紅血球之脂肪酸組成 ................................................................ 45
第三節、 抗氧化功能之探討 ........................................................................................ 46
一、 補充紅麴製品與血漿中輔酶Q10 的濃度 ......................................................... 46
二、 補充紅麴製品對於血漿或紅血球維生素E 濃度之影響 ................................ 47
三、 補充紅麴製品及併用輔酶Q10 對於MDA 的影響 ........................................... 48
四、 併用輔酶Q10 與紅麴製品對於LDL 氧化延遲時間的影響 ............................. 50
第四節、 肝腎功能及其他生化數值之探討 ................................................................ 51
第六章、 結 論 .........................................................................................................52
參考資料 ................................................................................................................... 84
附 錄 ................................................................................................................... 89
A. 受試者同意書 ............................................................................................................ 89
B. 基本資料問卷 ............................................................................................................ 91
C. 三天飲食紀錄表 ........................................................................................................ 92
D. 人體(臨床)試驗計畫審核同意書 ............................................................................. 94

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