褐藻岩藻黄素调控胆固醇代谢的机制研究

Fucoxanthin,a characteristic carotenoid found in brown algae,has been proven with preventing obesity and hypolipidemic activity. Since brown algae resources are very rich in China,it will improve our country's development level of brown algae's deep processing industry to study on the mechanism of regulating cholesterol metabolism by fucoxanthin from brown algae. As lacking of research on the mechanism, the project will combine in vivo and in vitro tests to investigate the regulatory effects of fucoxanthin on cholesterol metabolism and its molecule mechanism which will be explored from gene transcription and cytokine modulation level.Using hyperlipidemia rat's liver and HepG2 cells for the study, gene expression and protein levels of key enzymes and transcription factor including HMG-CoA-S, HMG-CoA-R and SREBP2 associated with fucoxanthin cholesterol synthesis, protein including LDLR and ACAT associated with cholesterol absorption and transport, the conversion rate-limiting enzyme of cholesterol to bile acids CYP7A1 will be measured by PCR and Western Blotting,which will clarify the mechanism of regulating cholesterol metabolism by fucoxanthin from brown algae.The results of this research will provide the theoretical basis and technical support to in-depth application of fucoxanthin in food, health products and pharmaceutical products.

岩藻黄素是褐藻所特有的一种类胡萝卜素。岩藻黄素具有很好的减肥降脂的生物活性。我国藻类资源十分丰富，开展岩藻黄素调节胆固醇代谢的作用机制研究，将有助于提高我国褐藻精深加工业的发展水平。针对目前对岩藻黄素调控胆固醇代谢作用机制缺乏研究的现状，本项目将结合体内和体外试验，从基因转录调节和细胞因子调控水平上探讨岩藻黄素调控胆固醇代谢的作用机制。项目分别以高脂血症大鼠的肝脏和肝癌HepG2细胞为研究对象，利用PCR和Western Blotting技术，研究岩藻黄素对胆固醇合成的关键酶及转录因子HMG-CoA-S、 HMG-CoA-R及 SREBP2，胆固醇吸收运输的相关蛋白LDLR及ACAT, 胆固醇向胆汁酸转化的限速酶CYP7A1的基因表达和蛋白水平，从而阐明岩藻黄素调控胆固醇代谢的作用机制，为其在食品、保健品和医药产品的深入应用提供理论依据和技术支撑。

岩藻黄素是褐藻所特有的一种类胡萝卜素，其具有很好的减肥降脂活性。针对目前对岩藻黄素调控胆固醇代谢作用机制缺乏研究的现状，本项目结合体内和体外试验，从基因转录调节和细胞因子调控水平上探讨岩藻黄素调控胆固醇代谢的作用机制。项目分别以高脂血症小鼠、大鼠及肝癌HepG2细胞为研究对象，利用PCR和Western Blotting技术，研究了岩藻黄素对胆固醇合成的关键酶及转录因子HMG-CoA-R及 SREBP2，胆固醇吸收运输的相关蛋白LDLR，ACAT2,ABCA1及LCAT, 胆固醇向胆汁酸转化限速酶CYP7A1及LXRα的基因表达和蛋白水平，从而阐明了岩藻黄素调控胆固醇代谢的作用机制，为其在食品、保健品和医药产品的深入应用提供理论依据和技术支撑。研究结果表明岩藻黄素对胆固醇代谢的调控机制为：岩藻黄素可通过上调SREBP2的表达，使其与HMG-COA-R基因相结合,下调HMG-COA-R基因,控制了胆固醇的合成速度，SREBP水解后以活性形式转移至细胞核中，与LDLR编码基因上游启动子序列结合，从而启动下游LDLR基因的表达，促进胆固醇的快速代谢；同时岩藻黄素抑制了动物肝组织中ACAT的表达，使得游离胆固醇无法与长链脂肪酸连接生成胆固醇酯，从而抑制了肝脏胆固醇的吸收。岩藻黄素通过上调LCAT基因的表达量从而催化合成成熟的HDL，并通过下调ABCA1基因，防止HDL-C从细胞内排出，导致动物体内HDL-C水平有所增加。细胞体外实验结果证实了固醇调节元件结合蛋白 (SREBP) 途径调节胆固醇代谢。本项目目前已发表中文核心期刊论文3篇，会议论文1篇，制定地方标准1项，培养硕士研究生4人。