辛伐他汀和格列齐特与牛血清白蛋白协同作用的光谱法研究

Spectroscopic investigation of the synergy between simvastatin and gliclazide as well as bovine serum albumin

采用荧光光谱、圆二色谱技术,研究了两种药物辛伐他汀(Sim)、格列齐特(Gli)在模拟生理条件下对牛血清白蛋白(BSA)的共同作用。结果表明,两种药物对BSA的内源荧光都有猝灭作用,它们共同作用不改变静态猝灭方式。由定位剂竞争实验知,Sim、Gli在BSA上的主要结合部位在siteⅠ。相比较单一的药物,两药物共存使研究目标药物与BSA结合常数减小,血液中游离浓度增大,促进了药物释放,且三元体系中Hill系数均小于1,表明两药物间存在负协同作用。同步荧光结果表明,协同作用对BSA的构象产生影响,使色氨酸残基微环境的极性增强。圆二色谱显示了两药物共存对BSA二级结构的变化产生不同的影响。

Under the simulative human physiological condition,the interaction of the simvastatin（ Sim） ,gliclazide（ Gli） and the bo-vine serum albumin（ BSA） were investigated by fluorescence spectra,Circular Dichroism. The results showed that drugs quenching the intrinsic fluorescence of the BSA,the joint action of the two drugs do not change the static quenching method. The competitive experiments suggest that the primary binding site for Sim and Gli are located on siteⅠof BSA. Compared to a single drug,the re-search objective drug and BSA binding constant decrease when two drugs coexistence. Therefore,free drug concentration at targets would increase,improving the efficacy of the drugs. Hill’s coefficients of the ternary systems are less than 1. It showed that the nega-tive cooperativity is found when Sim and Gli bound to BSA simultaneously. From the synchronous fluorescence,it was found that the synergy between Sim and Gli change the conformation of BSA. According to the CD,the secondary structure of BSA changed when two drugs coexistence.