簡易檢索 / 詳目顯示

研究生: 伍佳錞
Wu, Chia-Chun
論文名稱: 海洋深層水有機萃取物對高血脂倉鼠之降血脂效果
The Hypolipidemic Effect of Deep Sea Water-Dissolved Organic Matter on Hyperlipidemia Hamsters
指導教授: 鄭劍廷
Chien, Chiang-Ting
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2019
畢業學年度: 107
語文別: 英文
論文頁數: 60
中文關鍵詞: 高血脂海洋深層水非酒精性脂肪肝動脈硬化
英文關鍵詞: hyperlipidemia, deep sea water, non-alcoholic fatty liver disease, atherosclerosis
DOI URL: http://doi.org/10.6345/NTNU201900375
論文種類: 學術論文
相關次數: 點閱:154下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  •   高血脂(Hyperlipidemia)為造成肝臟及心血管疾病的危險因子,如非酒精性脂肪肝(Non-alcoholic fatty liver disease, NAFLD)與動脈硬化(Atherosclerosis)。高血脂起因於代謝性疾病或不均衡的飲食習慣。海洋深層水(Deep sea water, DSW)含有豐富的營養素,並具有抗氧化與抗發炎等特性。目前為止已有許多研究證明能預防或改善疾病。本篇研究欲探討飲用海洋深層水有機萃取物質調整血脂肪之成效。
      實驗設計分為一般飼料控制組、高脂飼料高血脂誘發組,以及高脂飼料搭配高低劑量海洋深層水有機萃取物治療組,一共四個組別。高脂肪飲食引發高血脂、非酒精性脂肪肝與初期動脈硬化。飲用海洋深層水有機萃取物質有效抑制血脂上升,減少脂肪於肝臟累積並降低細胞凋亡蛋白表現。低密度脂蛋白氧化堆積於血管內皮易導致動脈硬化。海洋深層水有機萃取物質為一卓越的抗氧化劑,使血液中的自由基與脂質氧化物顯著降低。此外,海洋深層水有機萃取物質抑制細胞黏附因子於動脈內皮表現,降低血管阻塞風險。
      透過有機萃取物所具備的抗氧化力與降低血脂的能力,能有效預防高血脂、肝臟與心血管疾病。

    Hyperlipidemia is a well-known risk factor for non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) like hypertension, atherosclerosis and stroke. Unbalanced eating habit or metabolic disorders lead to hyperlipidemia. Elevated blood cholesterol and triglyceride (TG) levels are important indicators of hyperlipidemia.
    Deep sea water (DSW) is characterized by abundant nutrients, antioxidant and anti-inflammatory effects. So far, DSW has been reported for therapeutic effects on several diseases. This study evaluated the therapeutic effect of DSW-dissolved organic matter (DSW-DOM) on hyperlipidemia hamsters.
    Animals were divided into four groups: normal diet (CON), high fat/cholesterol diet (HCD) and high fat/cholesterol diet with low or high dose of DSW-DOM (HCD-LD, HCD-HD). High fat/cholesterol diet caused hyperlipidemia, NAFLD and early atherosclerosis. DSW-DOM inhibited lipid profile elevation, reduced lipid accumulation and hepatic apoptosis. Buildup of oxidized low-density lipoprotein (ox-LDL) in endothelial cells caused atherosclerosis. DSW-DOM significantly reduced blood reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, DSW-DOM inhibited expression of adhesion molecules on endothelium, reducing the risk of thrombosis.
    The anti-oxidant and hypolipidemic effects of DSW-DOM prevent hyperlipidemia, NAFLD and CVD.

    I. 摘要 3 II. Abstract 4 III. Abbreviations 5 IV. Introduction 8 1. Hyperlipidemia 8 1.1 Hyperlipidemia and non-alcoholic fatty liver disease (NAFLD) 8 1.2 Hyperlipidemia and atherosclerosis 9 2. Deep sea water (DSW) 10 2.1 DSW improves cholesterol profiles 10 2.2 DSW prevents atherosclerosis 11 2.3 DSW prohibits cardiovascular problems 11 2.4 Deep sea water-dissolved organic matter (DSW-DOM) 12 3. Hyperlipidemia hamster model 12 V. Materials and methods 14 1. Animals 14 1.1 Golden Syrian hamsters 14 1.2 Grouping 14 2. Preparation of deep sea water-dissolved organic matter (DSW-DOM) 15 3. Hydrogen peroxide (H2O2) scavenging capacity of DSW-DOM 15 4. Blood lipid analysis 16 5. Triglyceride (TG) colorimetric assay 16 6. Ferric chloride (FeCl3)-induced acute arterial thrombosis 17 7. Platelet adhesiveness detection 18 8. Blood reactive oxygen species (ROS) detection 19 9. Malondialdehyde (MDA) assay 19 10. Histological analysis 20 10.1 Hematoxylin and Eosin stain 20 10.2 Oil red O stain 20 11. Immunohistochemistry 21 12. Western Blot 22 13. Statistical analysis 23 VI. Results 24 1. Hydrogen Peroxide (H2O2) Scavenging Capacity of DSW-DOM 24 2. Body weight 24 3. Food intake and feces 24 4. Lipid profile 25 5. Hepatic and fecal triglyceride concentration 25 6. Acute arterial thrombosis model of time to occlusion 26 7. Platelet adhesiveness detection in mesenteric arteries 26 8. Blood reactive oxygen species 26 9. Malondialdehyde (MDA) concentration in plasma 27 10. Histological analyses 27 11. Immunohistochemistry 27 12. Western blot 28 VII. Discussion 30 VIII. Conclusion 34 IX. References 35 X. Figure 41

    1. Chait A, Brunzell J: Acquired hyperlipidemia (secondary dyslipoproteinemias). Endocrinology and metabolism clinics of North America 1990, 19(2):259-278.
    2. Tsai T-Y, Chu L-H, Lee C-L, Pan T-M: Atherosclerosis-preventing activity of lactic acid bacteria-fermented milk− soymilk supplemented with Momordica charantia. Journal of agricultural and food chemistry 2009, 57(5):2065-2071.
    3. Baigent C, Blackwell L, Emberson J, Holland L, Reith C, Bhala N, Peto R, Barnes E, Keech A, Simes J: Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. In.: Elsevier; 2010.
    4. Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, Greenland P, Van Horn L, Tracy RP, Lloyd-Jones DM: Lifetime Risks of Cardiovascular Disease. New England Journal of Medicine 2012, 366(4):321-329.
    5. Harchaoui K, Visser M, Kastelein J, Stroes E, Dallinga-Thie G: Triglycerides and cardiovascular risk. Current cardiology reviews 2009, 5(3):216-222.
    6. Lee K-S, Kwon Y-S, Kim S, Moon D-S, Kim HJ, Nam K-S: Regulatory mechanism of mineral-balanced deep sea water on hypocholesterolemic effects in HepG2 hepatic cells. Biomedicine & Pharmacotherapy 2017, 86:405-413.
    7. Mills SJ, Harrison SA: Comparison of the natural history of alcoholic and nonalcoholic fatty liver disease. Current Gastroenterology Reports 2005, 7(1):32-36.
    8. Serviddio G, Bellanti F, Vendemiale G: Free radical biology for medicine: learning from nonalcoholic fatty liver disease. Free Radical Biology and Medicine 2013, 65:952-968.
    9. Zhu X, Yan H, Xia M, Chang X, Xu X, Wang L, Sun X, Lu Y, Bian H, Li X: Metformin attenuates triglyceride accumulation in HepG2 cells through decreasing stearyl-coenzyme A desaturase 1 expression. Lipids in health and disease 2018, 17(1):114.
    10. Adams LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK: NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. The American journal of gastroenterology 2009, 104(4):861.
    11. Wesolowski SR, El Kasmi KC, Jonscher KR, Friedman JE: Developmental origins of NAFLD: a womb with a clue. Nature Reviews Gastroenterology and Hepatology 2017, 14(2):81.
    12. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M: Global epidemiology of nonalcoholic fatty liver disease—meta‐analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016, 64(1):73-84.
    13. Libby P, Ridker PM, Hansson GK: Progress and challenges in translating the biology of atherosclerosis. Nature 2011, 473(7347):317.
    14. Davignon J, Ganz P: Role of endothelial dysfunction in atherosclerosis. Circulation 2004, 109(23 suppl 1):III-27-III-32.
    15. Korporaal SJ, Akkerman J-WN: Platelet activation by low density lipoprotein and high density lipoprotein. Pathophysiology of haemostasis and thrombosis 2006, 35(3-4):270-280.
    16. Gawaz M, Langer H, May AE: Platelets in inflammation and atherogenesis. The Journal of clinical investigation 2005, 115(12):3378-3384.
    17. Yamada Y, Doi T, Hamakubo T, Kodama T: Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system. Cellular and Molecular Life Sciences CMLS 1998, 54(7):628-640.
    18. Lusis AJ: Atherosclerosis. Nature 2000, 407:233.
    19. Nakasone T, Akeda S: The application of deep sea water in Japan. In: Proc 28th UJNR Aquac Panel Symp, UJNR Technical Report: 1999. 69-75.
    20. Miyamura M, Yoshioka S, Hamada A, Takuma D, Yokota J, Kusunose M, Kyotani S, Kawakita H, Odani K, TsUTSUI Y: Difference between deep seawater and surface seawater in the preventive effect of atherosclerosis. Biological and Pharmaceutical Bulletin 2004, 27(11):1784-1787.
    21. Kimata H, Tai H, Nakagawa K, Yokoyama Y, Nakajima H, Ikegami Y: Improvement of skin symptoms and mineral imbalance by drinking deep sea water in patients with atopic eczema/dermatitis syndrome (AEDS). ACTA MEDICA-HRADEC KRALOVE- 2002, 45(2):83-84.
    22. Hwang HS, Kim HA, Lee SH, Yun JW: Anti-obesity and antidiabetic effects of deep sea water on ob/ob mice. Marine biotechnology 2009, 11(4):531.
    23. Yoshioka S, Hamada A, Cui T, Yokota J, Yamamoto S, Kusunose M, Miyamura M, Kyotani S, Kaneda R, Tsutsui Y: Pharmacological activity of deep-sea water: examination of hyperlipemia prevention and medical treatment effect. Biological and Pharmaceutical Bulletin 2003, 26(11):1552-1559.
    24. Katsuda S-i, Yasukawa T, Nakagawa K, Miyake M, Yamasaki M, Katahira K, Mohri M, Shimizu T, Hazama A: Deep-sea water improves cardiovascular hemodynamics in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits. Biological and pharmaceutical Bulletin 2008, 31(1):38-44.
    25. Chen I-S, Chang Y-Y, Hsu C-L, Lin H-W, Chang M-H, Chen J-W, Chen S-S, Chen Y-C: Alleviative effects of deep-seawater drinking water on hepatic lipid accumulation and oxidation induced by a high-fat diet. Journal of the Chinese Medical Association 2013, 76(2):95-101.
    26. Ha BG, Shin EJ, Park J-E, Shon YH: Anti-diabetic effect of balanced deep-sea water and its mode of action in high-fat diet induced diabetic mice. Marine drugs 2013, 11(11):4193-4212.
    27. Fu Z-Y, Yang FL, Hsu H-W, Lu Y-F: Drinking deep seawater decreases serum total and low-density lipoprotein–cholesterol in hypercholesterolemic subjects. Journal of medicinal food 2012, 15(6):535-541.
    28. Hsu C-L, Chang Y-Y, Chiu C-H, Yang K-T, Wang Y, Fu S-G, Chen Y-C: Cardiovascular protection of deep-seawater drinking water in high-fat/cholesterol fed hamsters. Food chemistry 2011, 127(3):1146-1152.
    29. Sheu M-J, Chou P-Y, Lin W-H, Pan C-H, Chien Y-C, Chung Y-L, Liu F-C, Wu C-H: Deep sea water modulates blood pressure and exhibits hypolipidemic effects via the AMPK-ACC pathway: an in vivo study. Marine drugs 2013, 11(6):2183-2202.
    30. CHANG MH, TZANG BS, YANG TY, HSIAO YC, YANG HC, CHEN YC: EFFECTS OF DEEP‐SEAWATER ON BLOOD LIPIDS AND PRESSURE IN HIGH‐CHOLESTEROL DIETARY MICE. Journal of food biochemistry 2011, 35(1):241-259.
    31. He S, Hao J, Peng W, Qiu P, Li C, Guan H: Modulation of lipid metabolism by deep-sea water in cultured human liver (HepG2) cells. Marine biotechnology 2014, 16(2):219-229.
    32. Nani M, Zura S, Majid F, Jaafar A, Mahdzir A, Musa M: Potential health benefits of deep sea water: A review. Evidence-Based Complementary and Alternative Medicine 2016, 2016.
    33. SHEN JL, HSU TC, CHEN YC, HSU JD, YANG LC, TSAI FJ, LI CC, CHENG YW, HUANG CY, TZANG BS: Effects of deep‐sea water on cardiac abnormality in high‐cholesterol dietary mice. Journal of Food Biochemistry 2012, 36(1):1-11.
    34. Radhakrishnan G, Yamamoto M, Maeda H, Nakagawa A, KatareGopalrao R, Okada H, Nishimori H, Wariishi S, Toda E, Ogawa H: Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression. Biochemical and biophysical research communications 2009, 387(1):25-30.
    35. Huang W-C, Lin C-L, Hsu Y-J, Chiu Y-S, Chen Y-M, Wu M-F, Huang C-C, Wang M-F: Inulin and fibersol-2 combined have hypolipidemic effects on high cholesterol diet-induced hyperlipidemia in hamsters. Molecules 2016, 21(3):313.
    36. Dillard A, Matthan NR, Lichtenstein AH: Use of hamster as a model to study diet-induced atherosclerosis. Nutrition & metabolism 2010, 7(1):89.
    37. Dorfman SE, Smith DE, Osgood DP, Lichtenstein AH: Study of diet-induced changes in lipoprotein metabolism in two strains of Golden-Syrian hamsters. The Journal of nutrition 2003, 133(12):4183-4188.
    38. Srivastava RAK, He S: Anti-hyperlipidemic and insulin sensitizing activities of fenofibrate reduces aortic lipid deposition in hyperlipidemic Golden Syrian hamster. Molecular and cellular biochemistry 2010, 345(1-2):197-206.
    39. Dalbøge LS, Pedersen PJ, Hansen G, Fabricius K, Hansen HB, Jelsing J, Vrang N: A hamster model of diet-induced obesity for preclinical evaluation of anti-obesity, anti-diabetic and lipid modulating agents. PloS one 2015, 10(8):e0135634.
    40. Chen D-L, Chen T-W, Chien C-T, Li P-C: Intravenous low redox potential saline attenuates FeCl3-induced vascular dysfunction via downregulation of endothelial H2O2, CX3CL1, intercellular adhesion molecule-1, and p53 expression. Translational Research 2011, 157(5):306-319.
    41. Robinson MA, Welsh DC, Bickel DJ, Lynch Jr JJ, Lyle EA: Differential effects of sodium nitroprusside and hydralazine in a rat model of topical FeCl3-induced carotid artery thrombosis. Thrombosis research 2003, 111(1-2):59-64.
    42. Eckly A, Hechler B, Freund M, Zerr M, Cazenave JP, Lanza F, Mangin P, Gachet C: Mechanisms underlying FeCl3‐induced arterial thrombosis. Journal of Thrombosis and Haemostasis 2011, 9(4):779-789.
    43. Yang C-C, Yao C-A, Lin Y-R, Yang J-C, Chien C-T: Deep-sea water containing selenium provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1. PloS one 2014, 9(7):e96006.
    44. Pessayre D, Berson A, Fromenty B, Mansouri A: Mitochondria in steatohepatitis. In: Seminars in liver disease: 2001. Copyright© 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New …: 057-070.
    45. Sviridov D, Nestel P: Dynamics of reverse cholesterol transport: protection against atherosclerosis. Atherosclerosis 2002, 161(2):245-254.
    46. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation 2002, 106(25):3143-3143.
    47. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif J-C, Waters DD: Effects of torcetrapib in patients at high risk for coronary events. New England journal of medicine 2007, 357(21):2109-2122.
    48. Investigators A-H: Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. New England Journal of Medicine 2011, 365(24):2255-2267.
    49. Tsompanidi EM, Brinkmeier MS, Fotiadou EH, Giakoumi SM, Kypreos KE: HDL biogenesis and functions: role of HDL quality and quantity in atherosclerosis. Atherosclerosis 2010, 208(1):3-9.
    50. Litvinov D, Mahini H, Garelnabi M: Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. North American journal of medical sciences 2012, 4(11):523.
    51. Haraguchi Y, Toh R, Hasokawa M, Nakajima H, Honjo T, Otsui K, Mori K, Miyamoto-Sasaki M, Shinohara M, Nishimura K: Serum myeloperoxidase/paraoxonase 1 ratio as potential indicator of dysfunctional high-density lipoprotein and risk stratification in coronary artery disease. Atherosclerosis 2014, 234(2):288-294.
    52. Kostapanos MS, Elisaf MS: High density lipoproteins and type 2 diabetes: emerging concepts in their relationship. World journal of experimental medicine 2014, 4(1):1.
    53. Stancu CS, Carnuta MG, Sanda GM, Toma L, Deleanu M, Niculescu LS, Sasson S, Simionescu M, Sima AV: Hyperlipidemia‐induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters. Molecular nutrition & food research 2015, 59(11):2293-2302.
    54. Pessayre D, Mansouri A, Fromenty B: V. Mitochondrial dysfunction in steatohepatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology 2002, 282(2):G193-G199.
    55. Shimizu I, Shimamoto N, Saiki K, Furujo M, Osaw K: Lipid Peroxidation in Hepatic Fibrosis. In.; 2012.
    56. Kojima H, Sakurai S, Uemura M, Fukui H, Morimoto H, Tamagawa Y: Mitochondrial abnormality and oxidative stress in nonalcoholic steatohepatitis. Alcoholism: Clinical and Experimental Research 2007, 31:S61-S66.
    57. Wang Y, Ausman LM, Russell RM, Greenberg AS, Wang X-D: Increased apoptosis in high-fat diet–induced nonalcoholic steatohepatitis in rats is associated with c-Jun NH2-terminal kinase activation and elevated proapoptotic Bax. The Journal of nutrition 2008, 138(10):1866-1871.
    58. Cao L, Quan X-B, Zeng W-J, Yang X-O, Wang M-J: Mechanism of Hepatocyte Apoptosis. Journal of Cell Death 2016, 9:JCD.S39824.
    59. Savage DB, Choi CS, Samuel VT, Liu Z-X, Zhang D, Wang A, Zhang X-M, Cline GW, Yu XX, Geisler JG: Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. The Journal of clinical investigation 2006, 116(3):817-824.
    60. Steinberg D: Low density lipoprotein oxidation and its pathobiological significance. Journal of Biological Chemistry 1997, 272(34):20963-20966.
    61. Steinberg D: The LDL modification hypothesis of atherogenesis: an update. Journal of lipid research 2009, 50(Supplement):S376-S381.
    62. Spady D, Woollett L, Dietschy J: Regulation of plasma LDL-cholesterol levels by dietary cholesterol and fatty acids. Annual review of nutrition 1993, 13(1):355-381.
    63. Harmon JT, Tandon NN, Hoeg JM, Jamieson G: Thrombin binding and response in platelets from patients with dyslipoproteinemias: increased stimulus-response coupling in type II hyperlipoproteinemia. Blood 1986, 68(2):498-505.
    64. Magwenzi S, Woodward C, Wraith KS, Aburima A, Raslan Z, Jones H, McNeil C, Wheatcroft S, Yuldasheva N, Febbriao M et al: Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade. Blood 2015, 125(17):2693-2703.
    65. Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, Jung S, Littman DR, Weber C, Ley K: Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nature medicine 2003, 9(1):61.

    無法下載圖示 本全文未授權公開
    QR CODE