为了探究美洛昔康与溶菌酶的作用机制, 在pH=7.40的实验条件下, 采用荧光光谱、同步荧光光谱和理论模建分析技术研究了类风湿性关节炎药物美洛昔康与溶菌酶分子之间的相互作用。结果表明, 美洛昔康能够以静态猝灭形式有效地猝灭溶菌酶的内源荧光, 形成1∶1的复合物, 并使溶菌酶的构象发生改变。热力学结果表明，美洛昔康-溶菌酶体系的主要作用力类型为疏水作用力。理论模建结果表明，该体系除疏水作用外还存在氢键作用，且美洛昔康被溶菌酶的活性氨基酸残基Glu35和Asp52包围, 结合作用改变了溶菌酶催化活性中心处氨基酸残基的微环境。当患者服用15 mg美洛昔康时, 美洛昔康与溶菌酶的蛋白结合率W(B)为3.71%~8.79%, 说明美洛昔康与溶菌酶的结合对溶菌酶自身抗炎、抗菌功能的影响不大, 体系药物结合率W(Q)为1.08%~1.14%, 说明溶菌酶与美洛昔康结合不会影响美洛昔康的药效。该研究从理论上证明了溶菌酶在血浆环境中与药物美洛昔康结合后, 对溶菌酶本身功能和美洛昔康的药效不会产生严重影响。

In order to explore the active mechanisms of meloxicam and lysozyme, the interaction between the molecules of rheumatoid arthritis drugs, meloxicam and lysozyme was studied using fluorescence spectroscopy, synchronous fluorescence spectroscopy and theoretical modeling analysis under the pH=7.40 experimental conditions. The results showed that meloxicam was able to effectively quench the endogenous fluorescence of lysozyme, forming a 1∶1 complex and changing the conformation of lysozyme. Thermodynamic results indicated that the main type of meloxicam-lysozyme system was a hydrophobic interaction. The results of theoretical modeling indicated that the system had hydrogen bonds in addition to hydrophobic interactions and that meloxicam was surrounded by the active amino acid residues Glu35 and Asp52 from the lysozyme, which changed the microenvironment of amino acid residues at the active center of the lysozyme. When a patient took meloxicam 15 mg, the protein binding rate of meloxicam to lysozyme W(B) was 3.71%~8.79%, indicating that the combination of meloxicam and lysozyme has little effect on anti-inflammatory and antibacterial function of lysozyme itself, and the system drug binding rate W(Q) was 1.08%~1.14%, indicating that the combination of lysozyme and meloxicam does not affect the efficacy of meloxicam. This study theoretically proved that lysozyme does not have a serious effect on its own function or the efficacy of meloxicam after it is combined with meloxicam in plasma.