泽泻醇类化合物调血脂作用及分子机制的研究
Study on Alisols Hypolipidemic Effect and Molecular Mechanism
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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。
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关键词:
- 泽泻醇类化合物 /
- TC、TG、HDL-C /
- LCAT /
- 同源建模 /
- 分子模拟
Abstract: 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.-
Key words:
- Alisol acetates /
- TC,TG,HDL-C /
- LCAT /
- homology modeling /
- molecular modeling
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