本文選題：頭孢曲松　切入點(diǎn)：頭孢唑林　出處：《光譜學(xué)與光譜分析》2017年04期 　論文類型：期刊論文

【摘要】：頭孢唑林(CFZ)屬第一代β-內(nèi)酰胺類半合成頭孢菌素,對(duì)革蘭氏陽(yáng)性菌和革蘭氏陰性菌均有較強(qiáng)的抗菌作用。頭孢曲松(CRO)屬第三代β-內(nèi)酰胺類廣譜抗生素,對(duì)敏感致病菌導(dǎo)致的疾病及手術(shù)后期感染預(yù)防有一定作用。人血清白蛋白(HSA)作為生物體內(nèi)循環(huán)系統(tǒng)中含量最豐富的蛋白質(zhì),可以與多種內(nèi)源性和外源性化合物可逆性結(jié)合,起到儲(chǔ)存和轉(zhuǎn)運(yùn)的作用。因此,研究CFZ和CRO與HSA的相互作用對(duì)了解CFZ和CRO的藥代動(dòng)力學(xué)行為具有重要意義。在模擬生理?xiàng)l件下,采用多種光譜法和分子對(duì)接技術(shù)研究CFZ和CRO與HSA的相互作用。結(jié)果表明,在298和310K條件下,CFZ和CRO與HSA分別形成復(fù)合物導(dǎo)致內(nèi)源熒光猝滅,猝滅機(jī)制均為靜態(tài)猝滅。在消除內(nèi)濾光影響下,HSA-CFZ和HSA-CRO體系的猝滅常數(shù)(KSV)和結(jié)合常數(shù)(Ka)均隨著溫度的升高而降低,結(jié)合位點(diǎn)數(shù)約為1。根據(jù)F錸ster能量轉(zhuǎn)移定律,CFZ和CRO與HSA結(jié)合距離分別為2.41和1.40nm。希爾系數(shù)(nH)值小于1,表明CFZ和CRO分別與HSA結(jié)合后存在藥物間負(fù)協(xié)同作用。熱力學(xué)參數(shù)(ΔH_(HSA-CFZ)=-22.67kJ·mol~(-1),ΔH_(HSA-CRO)=-39.56kJ·mol~(-1),ΔS_(HSA-CFZ)=-4.90J·mol~(-1)·K~(-1),ΔS_(HSA-CRO)=-37.28J·mol~(-1)·K~(-1))揭示,CFZ和CRO能自發(fā)地通過(guò)氫鍵和范德華力與HSA相結(jié)合。三維熒光光譜和圓二色譜法(CD)顯示CFZ和CRO使HSA的微環(huán)境和構(gòu)象發(fā)生改變。分子對(duì)接技術(shù)顯示CFZ和CRO均結(jié)合在HSA的siteⅠ結(jié)合位點(diǎn)上,與取代實(shí)驗(yàn)結(jié)果一致。本研究有助于了解CFZ和CRO在機(jī)體內(nèi)的作用機(jī)制及對(duì)HSA結(jié)構(gòu)和功能的影響。
[Abstract]:Cefazolin (CFZ) belongs to the first generation of 尾 -lactam semisynthetic cephalosporins and has a strong antibacterial effect against Gram-positive and Gram-negative bacteria. Ceftriaxone (CRO) belongs to the third generation of 尾 -lactam broad-spectrum antibiotics. Human serum albumin (HSA), as the most abundant protein in the circulatory system, can bind to many endogenous and exogenous compounds. Therefore, it is important to study the interaction between CFZ and CRO and HSA to understand the pharmacokinetic behavior of CFZ and CRO. The interaction of CFZ and CRO with HSA was studied by means of various spectroscopic methods and molecular docking techniques. The results showed that the formation of complexes between CFZ and CRO and HSA at 298 and 310 K resulted in endogenous fluorescence quenching, respectively. The quenching mechanism was static quenching. The quenching constants of HSA-CFZ and HSA-CRO decreased with the increase of temperature. The binding sites are about 1. According to the energy transfer law of F rhenium ster, the binding distance between HSA and CFZ is 2.41 and 1.40 nm, respectively. The Hill coefficient is less than 1, which indicates that there is a negative synergistic effect between CFZ and CRO after binding to HSA. (螖 HSA-CFZU -22.67 kJ 路mol-1C, 螖 HSA-CROU -39.56 kJ 路mol-1, 螖 SSA-CFZU -4.90 J 路mol-l) 路K-1, 螖 SSA-CROU -37.28 J 路mol-1) 路K ~ (-1) revealed that CFZ and CRO could spontaneously combine with HSA through hydrogen and van der Waals force. Three-dimensional fluorescence spectra and circular dichroic chromatography showed that CFZ and CRO changed the microenvironment and conformation of HSA. Molecular docking techniques showed that CFZ and CRO were both CFZ and CRO. Binding to the site I binding site of HSA, This study is helpful to understand the mechanism of CFZ and CRO in vivo and the effect on the structure and function of HSA.
【作者單位】： 中央民族大學(xué)生命與環(huán)境科學(xué)學(xué)院;中央民族大學(xué)北京市食品環(huán)境與健康工程技術(shù)研究中心;
【基金】：國(guó)家自然科學(xué)基金項(xiàng)目(21177163) 高等學(xué)校學(xué)科創(chuàng)新引智計(jì)劃項(xiàng)目(B08044) 中央民族大學(xué)一流大學(xué)一流學(xué)科建設(shè)項(xiàng)目(YLDX01013);中央民族大學(xué)學(xué)術(shù)團(tuán)隊(duì)建設(shè)項(xiàng)目(2015MDTD25C&13C) 建設(shè)世界一流大學(xué)(學(xué)科)和特色發(fā)展引導(dǎo)專項(xiàng)資金(2016) 2015年統(tǒng)籌推進(jìn)一流大學(xué)和一流學(xué)科建設(shè)經(jīng)費(fèi)(10301-0150200604) 一流大學(xué)一流學(xué)科建設(shè)過(guò)渡性經(jīng)費(fèi)專項(xiàng)資金項(xiàng)目(2016,博士)資助
【分類號(hào)】：R96;O657.3

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