高膽固醇血症是產生動脈粥樣硬化的危險因素，本研究旨在探討甾醇的氧化產物和植物化學物質在餵食高膽固醇食金黃地鼠模型中對脂蛋白代謝的影響及其相關機制。 / 本研究包含四個部分。食物中同時含有植物甾醇及其氧化產物。第一部分旨在研究β-穀甾醇（Si）、甾醇(St)、β-穀甾醇氧化產物(SiOP)和豆甾醇氧化產物(StOP)對金黃地鼠血脂的影響。本研究顯示，Si和St組能有效降低血總膽固醇（TC）、非高密度脂蛋白膽固醇（non-HDL-C）和甘油三酯（TAG）的水平，而SiOP和StOP則失去此能力。RT-PCR分析表明，Si和St而非SiOP和StOP，能下調腸道醯基輔酶A：膽固醇醯基轉移酶2（ACAT2）和微粒體甘油三酯轉移蛋白（MTP）的mRNA表達。Si和St而非SiOP和StOP能有效防止動脈粥樣硬，Si和St的動脈弓舒張能力強於對照組和SiOP、StOP組。 / 辣椒鹼是辣椒中的活性成分。本研究第二部分表明，辣椒鹼能降低TC，NON-HDL-C，TAG，而不影響高密度脂蛋白膽固醇。餵養辣椒鹼能增加糞便中總酸性固醇的排泄，此作用有可能是通過上調膽固醇7α-羥化酶（CYP7A1）和下調肝X受體α（LXRα）的基因表達來實驗。辣椒鹼可通過抑制COX-2基因表達來改善內皮依賴性收縮。 / 藍莓含有豐富的抗炎抗氧化劑，例如花青素。本研究第三部分表明，食物中添加0.5和1.0藍莓花青素能導致TC呈劑量效益地降低6-12%，其中還伴隨22-29的中性固醇和41-74%的膽汁酸排泄的增加。RT-PCR分析表明食物中添加的藍莓花青素能下調腸道Niemann-Pick C1 Like 1 (NPC1L1)，ACAT2，MTP， 腺苷三磷酸結合盒轉運體G8(ABCG8)和肝臟3-羥基-3-甲基戊二醯輔酶A還原酶(HMG-CoA Reductase)的基因表達。 / 芝麻素是芝麻種子中含有抗氧化活性的木脂素類化合物。本研究第四部分表明，在食物中添加芝麻素可有效調控TC和non-HDL-C，同時不影響TAG，並導致非高密度脂蛋白膽固醇與高密度脂蛋白膽固醇比例的下降。這有可能與膽汁酸排泄增加、CYP7A1基因的上調，LXR的下調有關。 / 綜上所述，本研究證實了植物甾醇、辣椒鹼、藍莓花青素和芝麻素降低血膽固醇的能力。與此同時，本研究還表明植物甾醇被氧化後將失去其降低膽固醇的能力。 / Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Functional foods that can lower or regulate cholesterol concentration are of interest to both public and scientific communities. The present study was to investigate the effects of phytosterols, phytosterol oxidation products (POPs), capsaicinoids, blueberry anthocyanins and sesamin on plasma cholesterol concentration using hamsters as a model. / The whole project consisted of four parts. Human diets contain both phytosterols and POPs. Part I was to examine the effect of β-sitosterol (Si), stigmasterol (St), β-sitosterol oxidation products (SiOP) and stigmasterol oxidation products (StOP) on plasma cholesterol concentration. Results showed both Si and St could reduce while SiOP and StOP lost the capacity of lowering plasma total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C) and triacylglycerols (TAG). Real-Time PCR analysis demonstrated Si and St but not SiOP and StOP down-regulated mRNA levels of intestinal acyl CoA: cholesterol acyltransferase 2 (ACAT2) and microsomal triglyceride protein (MTP). In addition, aortas from hamsters given diets containing Si and St relaxed better than those from the control and their corresponding SiOP- and StOP-treated hamsters, suggesting that Si and St not SiOP and StOP were beneficial in improving lipoprotein profile and aortic function. / Capsaicinoids refer to a group of pungent compounds that are the active components found in chili peppers. Part II was to investigate the cholesterol-lowering activity of capsaicinoids and the associated molecular mechanisms. Results demonstrated that capsaicinoids reduced plasma TC, non-HDL-C and TAG with high-density lipoprotein cholesterol (HDL-C) being unaffected. This was accompanied by an increase in the fecal excretion of total acidic sterols, possibly mediated by up-regulation of cholesterol 7α-hydroxylase (CYP7A1) and down-regulation of liver X receptor alpha (LXRα). Capsaicinoids could also improve the endothelium-dependent relaxations and reduce the endothelium-dependent contractions by inhibiting the gene expression of COX-2. / Blueberries are rich in anthocyanins. Results from Part III experiments demonstrated that dietary supplementation with 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12% in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 2229% and 4174%, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of intestinal Niemann-Pick C1-like 1 (NPC1L1), ACAT2, MTP, ABCG 8 and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase. / Sesamin is a major lignan in sesame seed and is known to exhibit antioxidative activity. Part IV was to investigate the mechanism by which sesamin decreased plasma cholesterol concentration. Results clearly demonstrated supplementation of sesamin into diets could favorably reduce serum TC and non-HDL-C with TAG being unaffected. In addition, dietary supplementation of 0.2 or 0.5% of sesamin could cause a significant decrease in the ratio of non-HDL-C to HDL-C. This was accompanied by a marked increase in bile acid excretion and up-regulation of CYP7A1 and down-regulation of LXRα. / In conclusion, phytosterols, capsaicinoids, blueberry anthocyanins and sesamin were beneficial in improving lipoprotein profile in hamsters fed a high-cholesterol diet. However, phytosterols lose the cholesterol-lowering capacity when they are oxidized. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liang, Yintong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 112-123). / Abstracts also in Chinese. / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- Cardiovascular diseases --- p.1 / Chapter 1.2 --- Cholesterol --- p.2 / Chapter 1.3 --- Lipoproteins --- p.4 / Chapter 1.4 --- Cholesterol homeostasis --- p.6 / Chapter 1.4.1 --- HMG-CoA reductase --- p.7 / Chapter 1.4.2 --- LDL receptor --- p.9 / Chapter 1.4.3 --- Intestine ACAT2 --- p.10 / Chapter 1.4.4 --- NPC1L1 --- p.11 / Chapter 1.4.5 --- CYP7A1 and LXRα --- p.12 / Chapter 1.4.6 --- SREBP2 --- p.14 / Chapter 1.4.7 --- ABCG5 and ABCG8 --- p.15 / Chapter 1.5 --- Phytochemicals --- p.16 / Chapter 1.5.1 --- Phytosterols --- p.16 / Chapter 1.5.2 --- Capsaicinoids --- p.17 / Chapter 1.5.3 --- Blueberry anthocyanins --- p.19 / Chapter 1.5.4 --- Sesamin --- p.20 / Chapter 1.6 --- Animal model --- p.22 / Chapter Chapter 2 --- Effect of Phytosterols and their Oxidation Products on Lipoprotein Profiles and Vascular Function / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Objective --- p.24 / Chapter 2.3 --- Materials and methods --- p.24 / Chapter 2.3.1 --- Preparation of sitosterol oxidation products (SiOP) and stigmasterol oxidation products (StOP) / Chapter 2.3.2 --- Diets --- p.25 / Chapter 2.3.3 --- Hamsters --- p.25 / Chapter 2.3.4 --- Analysis of individual SiOP and StOP in serum and liver --- p.26 / Chapter 2.3.5 --- Analysis of plasma lipoproteins --- p.28 / Chapter 2.3.6 --- Measurement of atherosclerotic plaque --- p.28 / Chapter 2.3.7 --- Analysis of cholesterol in the liver and aorta --- p.28 / Chapter 2.3.8 --- Determination of fecal neutral and acidic sterols --- p.29 / Chapter 2.3.9 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL receptor, HMG-CoA reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP. --- p.29 / Chapter 2.3.10 --- Western blotting analysis of hepatic SREBP2, LDL receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.32 / Chapter 2.3.11 --- Vascular reactivity --- p.32 / Chapter 2.4 --- Results --- p.34 / Chapter 2.4.1 --- Composition of SiOP and StOP --- p.34 / Chapter 2.4.2 --- Food intake, body and organ weights --- p.34 / Chapter 2.4.3 --- Plasma TC, HDL, non-HDL ,TAG, Non-HDL-C/HDL-C --- p.34 / Chapter 2.4.4 --- Aortic cholesterol and atherosclerotic plaque --- p.35 / Chapter 2.4.5 --- Liver cholesterol, SiOP and StOP --- p.35 / Chapter 2.4.6 --- Fecal neutral, acidic sterols and cholesterol balance --- p.35 / Chapter 2.4.7 --- Immunoblot and mRNA analysis --- p.36 / Chapter 2.4.8 --- Vascular reactivity --- p.36 / Chapter 2.4.9 --- Role of COX in endothelium-dependent contractions --- p.37 / Chapter 2.5 --- Discussion --- p.50 / Chapter Chapter 3 --- Cholesterol-Lowering Activity of Capsaicinoids Is Mediated by Increasing Sterol Excretion in Hamsters Fed a High Cholesterol Diet / Chapter 3.1 --- Introduction --- p.54 / Chapter 3.2 --- Objective --- p.55 / Chapter 3.3 --- Materials and methods --- p.55 / Chapter 3.3.1 --- Diets --- p.55 / Chapter 3.3.2 --- Hamsters --- p.57 / Chapter 3.3.3 --- Analysis of plasma lipoproteins --- p.57 / Chapter 3.3.4 --- Measurement of atherosclerotic plaque --- p.57 / Chapter 3.3.5 --- Analysis of cholesterol in the liver and aorta --- p.57 / Chapter 3.3.6 --- Determination of fecal neutral and acidic sterols --- p.57 / Chapter 3.3.7 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL receptor, HMG-CoA reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP --- p.57 / Chapter 3.3.8 --- Western blotting analysis of hepatic SREBP2, LDL receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.58 / Chapter 3.3.9 --- Vascular reactivity --- p.58 / Chapter 3.4 --- Results --- p.59 / Chapter 3.4.1 --- Food intake, body and organ weights --- p.59 / Chapter 3.4.2 --- Plasma TC, HDL, non-HDL,TAG, Non-HDL-C/HDL-C --- p.59 / Chapter 3.4.3 --- Aortic cholesterol and atherosclerotic plaque --- p.59 / Chapter 3.4.4 --- Fecal neutral, acidic sterols and cholesterol balance --- p.59 / Chapter 3.4.5 --- Immunoblot and mRNA analysis --- p.60 / Chapter 3.4.6 --- Vascular reactivity --- p.60 / Chapter 3.4.7 --- Role of COX in endothelium-dependent contractions --- p.61 / Chapter 3.5 --- Discussion --- p.74 / Chapter Chapter 4 --- Effect of Blueberry Anthocyanins on Lipoprotein Profiles in Hamsters Fed a Cholesterol Diet / Chapter 4.1 --- Introduction --- p.77 / Chapter 4.2 --- Objective --- p.78 / Chapter 4.3 --- Materials and methods --- p.78 / Chapter 4.3.1 --- HPLC analysis of blueberry anthocyanins --- p.78 / Chapter 4.3.2 --- Diet --- p.79 / Chapter 4.3.3 --- Hamsters --- p.80 / Chapter 4.3.4 --- Analysis of plasma lipoproteins --- p.80 / Chapter 4.3.5 --- Analysis of cholesterol in the liver --- p.80 / Chapter 4.3.6 --- Determination of fecal neutral and acidic sterols --- p.81 / Chapter 4.3.7 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL Receptor, HMG-CoA Reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP --- p.81 / Chapter 4.3.8 --- Western blotting analysis of hepatic SREBP2, LDL Receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.81 / Chapter 4.4 --- Results --- p.82 / Chapter 4.4.1 --- Food intake, body, and organ weights --- p.82 / Chapter 4.4.2 --- Plasma TC, HDL-C, non-HDL-C, and TAG --- p.82 / Chapter 4.4.3 --- Liver cholesterol concentration --- p.82 / Chapter 4.4.4 --- Fecal total sterols and apparent sterol retention --- p.82 / Chapter 4.4.5 --- Immunoblot and mRNA analysis --- p.83 / Chapter 4.5 --- Discussion --- p.92 / Chapter Chapter 5 --- Effect of Sesamin on Lipoprotein Profiles in Hamsters Fed a high Cholesterol Diet / Chapter 5.1 --- Introduction --- p.95 / Chapter 5.2 --- Objective --- p.95 / Chapter 5.3 --- Materials and methods --- p.96 / Chapter 5.3.1 --- Diets --- p.96 / Chapter 5.3.2 --- Hamsters --- p.96 / Chapter 5.3.3 --- Methods --- p.97 / Chapter 5.4 --- Results --- p.98 / Chapter 5.4.1 --- Food intake, body and organ weights --- p.98 / Chapter 5.4.2 --- Plasma TC, HDL-C, non-HDL-C ,TAG, Non-HDL-C/HDL-C --- p.98 / Chapter 5.4.3 --- Liver cholesterol --- p.98 / Chapter 5.4.4 --- Fecal neutral, acidic sterols and cholesterol balance --- p.98 / Chapter 5.4.5 --- Immunoblot and mRNA analysis --- p.99 / Chapter 5.5 --- Discussion --- p.109 / References --- p.112
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_328480 |
| Date | January 2012 |
| Contributors | Liang, Yintong., Chinese University of Hong Kong Graduate School. Division of Life Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | electronic resource, electronic resource, remote, 1 online resource (xi, 123 leaves) : ill. (some col.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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