光谱法研究穿琥宁与牛血清白蛋白的相互作用

Study on the Interaction between Potassium Dehydroandrograpolide Succinate with Bovine Serum Albumin by Spectroscopic Methods

摘要:

穿琥宁(PDS)是一种药物，被广泛用于治疗病毒性肺炎，病毒性上呼吸道感染等的消炎药，被誉为“中药抗生素”。在优化的实验条件下，运用荧光和紫外光谱法，在不同的温度下研究穿琥宁与牛血清白蛋白(BSA)的相互作用及共存金属离子的影响。用Stern-Volmer， Lineweaver–Burk 和 双对数方程计算了速率常数(Kq)，表观猝灭常数 (Ksv)，结合常数 (KA) ，静态荧光猝灭缔合常数(KLB) 和结合位点数(n)。结果表明：穿琥宁能结合BSA。由于生成PDS-BSA复合物，穿琥宁对BSA的猝灭是静态猝灭机理。热力学参数表明是一个自发过程，其作用力类型主要为静电作用力。至少一个结合位点。BSA 的亚螺旋域ⅡA和ⅢA是主要结合位置，离酪氨酸残基更近，无药物协同作用。穿琥宁对BSA构象产生影响。Pb2+、Mn2+、Ni2+和Cu2+对PDS与BSA结合产生竞争作用，增强药效。Cr3+对穿琥宁与BSA结合产生促进作用，延长药效时间。该研究结果对揭示药物动力学问题及新的抗病毒类中草药的研发提供了理论依据。

Abstract:

Dehydroandrograpolide Succinate (PDS) is a drug, widely used to treat viral pneumonia, viral upper respiratory tract infection such as anti-inflammatory drugs, known as the “Chinese medicine antibiotics”. Herein, Under the optimal conditions，fluorescence and absorption spectroscopy were used to study the interaction of PDS with bovine serum albumin (BSA) and effects of metal ions at different temperatures. The rate constant (Kq), apparent quenching constant (Ksv), binding constant (KA) and static fluorescence quenching association constant (KLB) and binding site number(n) were calculated using Stern-Volmer, Lineweaver–Burk and Double logarithm equations. The results show that PDS is able to bind to BSA. The probable quenching mechanism of BSA by PDS was mainly static quenching due to the formation of a PDS-BSA complex. The results of thermodynamic parameters indicate that electrostatic force plays the main role in the binding process and the binding process was spontaneous. The obtained data for binding sites of n approximately equal to 1 indicated that there was a single class of binding site for the BSA with PDS. The primary binding site for PDS was located at sub-domain ⅡA and ⅢA of BSA and near by tyrosine residue. There was almost no cooperative effect. The results obtained from synchronous fluorescence showed that the interaction between BSA and PDS caused the conformational changes of BSA. Pb2+, Mn2+, Ni2+and Cu2+ competed with the interaction of PDS with BSA, increasing medical effectiveness. Cr3+ promoted on interaction and prolonged drug effect time. The obtained results not only provided a theoretical basis for revealing the pharmacokinetics and further research on development of new anti virus herbs drugs.