摘要
目的研究泽泻调脂效应物质泽泻醇类化合物23-乙酰泽泻醇B、24-乙酰泽泻醇A对高脂小鼠调血脂作用及其分子机制。方法建立高脂小鼠模型,检测泽泻醇给药后的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C),检测了脂代谢关键酶卵磷脂胆固醇酰基转移酶(LCAT)的活性,通过同源建模得到LCAT分子结构,采用分子模拟进行了泽泻醇与LCAT相互作用的研究。结果泽泻醇降低TG、TC水平,升高HDL-C水平,起到调血脂作用。泽泻醇降低LCAT活性,与LCAT的结合区域在Leu201~Phe305范围内。结论泽泻醇升高HDL-C的机制可能非通过提高LCAT活性实现,Leu201~Phe305区域可能为其抑活位置。Ile227、Arg217、Gly229 3个氨基酸可能是2者与该蛋白相互作用的关键氨基酸残基。
OBJECTIVE To study the different effects and molecular mechanism of Alisol acetates(alisol B 23-acetate and alisol A 24-acetate)on the decrease of the hyperlipidemia of fat mice.METHODS Established a hyperlipidemic mice model,measured the level of TC,TG and HDL-C after the administration of Alisol acetates,detected the activity of LCAT,which is a key enzyme in lipid metabolism,obtained the molecular structure of LCAT by homology modeling and studied the interaction between LCAT and Alisol acetates using molecular modeling.RESULTS Alisol acetates played a hypolipidemic effect by reducing TG,TC level and increasing HDL-C level.lisol acetates decreased the LCAT activity.Alisol acetates binding regions are in the range of Leu201~Phe305.CONCLUSION Alisol acetates elevated HDL-C mechanism may not be by modulating LCAT activity.The region of Leu201~Phe305may be the suppression positions.Ile227,Arg217,Gly229 may be the critical amino acid residues for the interaction.
出处
《南京中医药大学学报》
CAS
CSCD
北大核心
2016年第5期451-455,共5页
Journal of Nanjing University of Traditional Chinese Medicine
基金
国家自然科学基金(81303173
81673534)
江苏省自然科学基金(BK20161576)
江苏省高校自然科学基金(14KJB360001)
江苏高校品牌专业建设工程资助项目(PPZY2015A070)