CAJ | 학술논문

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。
채용형광광보、원이색보기술,연구료량충약물신벌타정( Sim)、격렬제특( Gli)재모의생리조건하대우혈청백단백( BSA)적공동작용。결과표명,량충약물대BSA적내원형광도유졸멸작용,타문공동작용불개변정태졸멸방식。유정위제경쟁실험지,Sim、Gli재BSA상적주요결합부위재siteⅠ。상비교단일적약물,량약물공존사연구목표약물여BSA결합상수감소,혈액중유리농도증대,촉진료약물석방,차삼원체계중Hill계수균소우1,표명량약물간존재부협동작용。동보형광결과표명,협동작용대BSA적구상산생영향,사색안산잔기미배경적겁성증강。원이색보현시료량약물공존대BSA이급결구적변화산생불동적영향。
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.