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羟乙基淀粉130/0.4引起的载脂蛋白A-I结构变化揭示潜在毒性机制。

Structural Changes of Apolipoprotein A-I Caused by Hydroxyethyl Starch 130/0.4 Reveals Potential Toxic Mechanisms.

作者信息

Qu Lingyan, Jia Liqun, Zhang Jianzhong, Ni Shuqin

机构信息

Department of Anesthesiology, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, 264003, China.

Department of Anesthesiology, The 80th Army Hospital of People's Liberation Army, Weifang, 264008, China.

出版信息

Protein J. 2025 Aug 30. doi: 10.1007/s10930-025-10283-8.

DOI:10.1007/s10930-025-10283-8
PMID:40884741
Abstract

6% hydroxyethyl starch (HES 130/0.4) is frequently employed to address hypovolemia, ensuring sufficient organ perfusion and oxygen transport. The effects on Apolipoprotein A-I (ApoA-I) were examined at three temperatures-280, 295, and 310 K-through several spectroscopic techniques to explore its possible interaction with the predominant protein in veins. The experimental findings indicated that HES 130/0.4 efficiently extinguished the intrinsic fluorescence of APOA-I. We also assessed the binding sites, binding constant, and thermodynamic parameters, which indicated that HES 130/0.4 can spontaneously associate with APOA-I via hydrogen bonds and van der Waals interactions (ΔG =  - 1.93 × 10 J·mol, ΔH =  - 5.63 × 10 J mol⁻, and ΔS =  - 119 J mol⁻ K⁻) with a single binding site and week binding forces (n = 1.03 and K = 1.78 × 10 M) at body temperature. Moreover, the structure of APOA-I was significantly altered in the presence of HES 130/0.4. Blood Ca and Fe will diminish the storage duration. The study provides accurate and thorough foundational data to clarify the binding mechanisms of HES 130/0.4 with APOA-I in vitro, which may help the comprehension of its impact on protein function and toxic mechanism during transit and distribution in the bloodstream.

摘要

6%羟乙基淀粉(HES 130/0.4)常用于治疗血容量不足,以确保足够的器官灌注和氧气运输。通过几种光谱技术,在280、295和310 K这三个温度下研究了其对载脂蛋白A-I(ApoA-I)的影响,以探索其与静脉中主要蛋白质可能的相互作用。实验结果表明,HES 130/0.4能有效淬灭ApoA-I的内在荧光。我们还评估了结合位点、结合常数和热力学参数,结果表明,HES 130/0.4可通过氢键和范德华相互作用与ApoA-I自发缔合(ΔG = -1.93×10 J·mol,ΔH = -5.63×10 J mol⁻,ΔS = -119 J mol⁻ K⁻),在体温下具有单一结合位点且结合力较弱(n = 1.03,K = 1.78×10 M)。此外,在HES 130/0.4存在的情况下,ApoA-I的结构发生了显著改变。血液中的钙和铁会缩短储存时间。该研究提供了准确而全面的基础数据,以阐明HES 130/0.4与ApoA-I在体外的结合机制,这可能有助于理解其在血液中转运和分布过程中对蛋白质功能的影响及其毒性机制。

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