乙酰泽泻醇降低胆固醇分子机制研究

被引：12

作者：

徐飞 ^{[1
]}

陆彩 ^{[1
]}

吴启南 ^{[1
]}

于慧 ^{[2
]}

陈军 ^{[1
]}

谷巍 ^{[1
]}

机构：

[1] 南京中医药大学药学院

[2] 江苏省中医院血液科

来源：

中药新药与临床药理 | 2016年 / 27卷 / 06期

关键词：

乙酰泽泻醇; HMG-CoA还原酶; 试剂盒法; Western plotting; 分子模拟;

D O I：

10.19378/j.issn.1003-9783.2016.06.001

中图分类号：

R285.5 [中药实验药理];

学科分类号：

100806 [中药药理学];

摘要：

目的从分子水平探讨乙酰泽泻醇降低胆固醇(TC)的作用机理。方法利用试剂盒法测定了调脂中药泽泻主要有效成分23-乙酰泽泻醇B和24-乙酰泽泻醇A对高脂小鼠TC的影响,利用试剂盒法、Western blotting技术结合分子模拟技术研究两者对TC代谢关键酶3-羟基-3-甲基戊二酸单酰辅酶A(HMG-Co A)还原酶作用的分子机理。结果乙酰泽泻醇能显著降低高脂小鼠TC(P<0.01,P<0.05),23-乙酰泽泻醇B作用强度高于24-乙酰泽泻醇A(P<0.05),同时在体内、体外均可剂量依赖性下调HMG-Co A还原酶活性(P<0.01),且23-乙酰泽泻醇B对该酶作用强于24-乙酰泽泻醇A(P<0.05)。两者均未显著下调HMG-Co A还原酶的蛋白表达(P>0.05)。两者与HMG-Co A还原酶结合的关键氨基酸残基可能为Lys691、Asp767、Asn658。结论乙酰泽泻醇降低TC的机制可能是其原型药物通过抑制HMG-Co A还原酶活性来达到,且可能是通过直接竞争性与HMG-Co A还原酶结合抑制其作用,乙酰泽泻醇的舵手基团为其侧链,侧链与母环折叠结合弱,打开结合强。

引用

页码：737 / 745

页数：9

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