泽泻醇类化合物调血脂作用及分子机制的研究

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。 

Study on Alisols Hypolipidemic Effect and Molecular Mechanism

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~Phe305 may be the suppression positions. Ile227， Arg217， Gly229 may be the critical amino acid residues for the interaction.