目的 何首乌是具有良好的降脂活性的重要云药,二苯乙烯苷(TSG)是其主要活性成分,阐明二苯乙烯苷调节脂代谢的机制,为何首乌进一步更深层的研究奠定基础。方法 采用含医用脂肪乳的培养液诱导肝L-02细胞48 h,建立肝细胞脂肪变性模型,给予二苯乙烯苷不同浓度刺激液进行培养,采用洛伐他汀、非诺贝特为阳性对照。24 h后测定肝细胞内甘油三酯(TG)、胆固醇(TC)及其体内合成、分解途径中关键酶及蛋白含量。结果 二苯乙烯苷可将脂肪化肝L-02细胞中甘油三酯含量降低约40%,胆固醇含量降低约55%;可使甘油三酯合成关键酶(DGAT)、胆固醇合成关键酶(HMG-CoA还原酶)含量降至正常细胞水平;可升高胆固醇分解关键酶(CYP7A) 含量约50%,能将甘油三酯分解关键酶(HTGL)含量提升近8倍;同时可明显降低游离脂肪酸在体内的结合蛋白(L-FABP)、转运蛋白(FATP-4)的表达量,进而限制体内甘油三酯合成的原料供应。结论 何首乌主要活性成分二苯乙烯苷对甘油三酯、胆固醇的合成、分解及转运的多个关键酶或关键蛋白均有良好的调控作用,具有较好的降脂活性。
Abstract
OBJECTIVE To elucidate the mechanism of the active chemical substance of Radix Polygoni Multiflori which is an important Yunyao with lipid-lowering activity, 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), for regulating lipid metabolism, thus making a foundation for further studies of Radix Polygoni Multiflori. METHODS The steatosis model was established by exposuring L-02 hepatocytes in fat emulsion for 48 h. The effects of TSG on the contents and activities of key enzymes and proteins in the synthesis and decomposition pathways of triglyceride (TG) and cholesterol (TC) were investigated. RESULTS After the exposure to TSG, the intracellular contents of TG and TC in hepatic L02 cells reduced by about 40% and 55%; DGAT and HMG-CoA reductase contents decreased to ordinary levels; CYP7A and HTGL levels increase by 50% and almost 8 times, respectively. Meanwhile, TSG significantly reduced the expression of liver type fatty acid binding protein (L-FABP) and fatty acid transport protein 4 (FATP-4), which could limit the supply of materials for TG synthesis in vivo. CONCLUSION TSG shows god TC and TG reducing effects by affecting the synthesis and decomposition pathways of TG and TC.
关键词
何首乌 /
二苯乙烯苷 /
脂质 /
合成酶 /
分解酶 /
转运蛋白
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Key words
Radix Polygoni Multiflori /
TSG /
lipid /
synthetase /
decomposition enzyme /
transport protein
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中图分类号:
R965
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参考文献
[1] WANG W J, XUE Y M, ZHAO R H, et al. Progress of chemical composition and pharmacological of Padix Polygoni Multiflori. J Yunnan Univ Tradit Chin Med(云南中医学院学报), 2007, 30(3):60-64. [2] Ch P (2010) VolⅠ(中国药典2010年版. 一部). 2010: 164.[3] ZHANG X S, LIU Q L. Effects of Padix Polygoni Multiflori on lipid-lowering and anti-atherosclerotic . Int Med Health Guid News(国际医药卫生导报), 2007, 13(16):155-157.[4] WANG X S, XIE G Y, SHI X L, et al. The effect of different kinds of Chinese herb medicine such as Padix Polygoni Multiflori on blood biochemical indexes in rats of fatty liver. J Anhui Tradit Chin Med Coll(安徽中医学院学报), 2006, 25(5): 39-40.[5] FANG W, QIN Y W, WANG L Y, et al. The protecting effect of PMTG on the Atherosclerotic Lesion Formation. Chin J Drug Appl Monitor(中国药物应用与监测), 2005,2(1): 48-51.[6] LI F F, SONG S J, LIU K. Effects of stilbene glucoside on experimental hyperlipidemia model. J Hebei Med Univ(河北医科大学学报), 2004, 25(5): 260-262.[7] LI L C, WU X D, TIAN W X. Inhibition to fatty acid synthase with extract of tuber fleeceflower root. Chin J Biochem Mol Biol(中国生物化学与分子生物学报), 2003, 9(3): 297-304.[8] TANG G Y, LIU Z J, SHAN L. Progress of diacylglycerol acyltransferase (DGAT) study. Chin J Oil Crop Sci(中国油料作物学报), 2010,32(2):320-328.[9] WANG L L, PENG Z Y, SHAO Y Y, et al. Progress of the study of plant diacylgycerol acyltransgerase (DGAT) gene. Acta Bot Boreali-Occidentalia Sin(西北植物学报), 2009, 29(9):1924-1931. WANG W, TONG T J. The key enzyme of cholesterol synthesis pathway: HMG-CoA reductase and Disease . Prog Physiol Sci(生理科学进展), 1999, 30(1):7-11. CUI G Z, FEN Y L, LI N, et al. Catalytic mechanism and characteristics of HMG-CoA reductase . J Med Mol Biol(医学分子生物学杂志), 2008, 31(6):542-545. XIE X Z, ZHAO S P. Polymorphism of hepatic lipase gene and blood lipid and coronary heart disease . Chin J Arterioscler(中国动脉硬化杂志), 2005, 13(3):383-386. ZHANG R, CUI R Z, LI Z C. Synthesis, structure and function of hepatic lipase. Molecular Cardiology of China(中国分子心脏病学杂志), 2006,6(2):111-114. CAO Y, BEI W J. Research progress of the regulation to cholesterol 7α-hydroxylase related to lipid metabolism. Acad J Guangdong Coll Pharm(广东药学院学报), 2011,27(6):658-661. FAN H, GUO J. Current studies on bioactive components regulating cholesterol 7α-hydroxylase . Chin New Drugs J(中国新药杂志), 2011, 20(8):692-696. CHEN F R, ZHANG Y W, ZHANG N, et al. Research progress of low-density lipoprotein cholesterol and atherosclerosis . Mod J Int Chin Tradit West Med(现代中西医结合杂志), 2010, 19(10):1294-1297. GAO Y Y, WU H Q. Progress of reduce low-density lipoprotein cholesterol mechanisms. Stroke and Nervous Diseases(中风与神经疾病杂志), 2012, 29(4):253-255. WEN Z G, HOU S S, XIE M, et al. Research progress of synthetic and secrete very low density lipoprotein . Chin J Animal Nut(动物营养学报), 2011, 23(11):1854-1861. SHAN Y H. Research progress of very low density lipoprotein and lipid metabolism . J Med Res(医学研究杂志), 2012, 10:185-187. HU W L. Research progress of high-density lipoprotein cholesterol resistant atherosclerosis. Foreign Med Sci (Sec Int Med)(国外医学 内科学分册), 2003, 30(6):235-238,248. YU Y X, CHEN B W, SHANG E N, et al. Research progress of high-density lipoprotein drug regulation . Chin J Pharm Toxicol(中国药理学与毒理学杂志), 2010,24(4):311-316. KRAMMER J, MARGARETE D, EHEHALT F, et al. Overexpression of CD36 and Acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells . Int J Med Sci(国际医学科学杂志), 2011, 8: 599-614. FENG A J, CHEN D F. The expression and the significance of L-FABP and FATP4 in the development of nonalcoholic fatty liver disease in rats. Chin J Hepatol(中华肝脏病杂志), 2005, 13(10):776-779. HIGUCHI N, KATO M, TANAKA M, et al. Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease . Exp Therapeu Med, 2011, 2: 1077-1081.
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脚注
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基金
国家自然科学基金资助项目(81260553;81460623);云南省应用基础研究重点项目(2014FA035);云南省应用基础研究面上项目(2012FD043)
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