阿托伐他汀与人血清白蛋白相互作用机制的研究

Analysis on interaction between human serum albumin and atorvastatin

目的模拟人体生理条件(p H 7.4)下阿托伐他汀(atorvastatin)和人血清白蛋白(HSA)的相互作用的过程。方法采用圆二色谱、荧光光谱、等温滴定量热法和分子对接模拟法,测定结合方式、结合位点数、热力学参数和分子结合距离等相关信息。结果在25℃下,随着atorvastatin逐渐加入到HSA中,α-螺旋含量从58.34%逐渐减少到28.13%(Catorvastatin/CHSA=10.0);atorvastatin以静态淬灭的方式淬灭了HSA的内源性荧光;通过疏水-疏水和氢键作用结合了血清白蛋白且结合比为1∶1;分子对接结果表明,与HSA最有可能的结合位点为214位色氨酸残基附近。结论为阐述他汀类药物的药代动力学行为机制提供科学依据。

Objective To study the interaction between atorvastatin and human serum albumin(HSA).Methods The binding constants,binding site numbers,thermodynamic parameters and binding distance were measured using CD,fluorescence spectroscopy,ITC and molecular docking technique.Results Theα-helix content in HSA decreased from 58.34%(C HSA/C atorvastatin=0)to 28.13%(C HSA/C atorvastatin=10.0)by the atorvastatin interaction with HSA.Atorvastatin could quench the intrinsic fluorescence of HSA through a static quenching procedure.Both hydrogen bonds and vander Waals interactions played major roles in the binding of atorvastatin to HSA by forming a 1∶1 type non-covalent complex.Conclusion This finding perhaps reflects the store and transport process of Statin in the body and the mechanism of action.