血清白蛋白的功能、应用及纯化工艺研究进展

doi:10.16431/j.cnki.1671-7236.2023.06.010

摘要/Abstract

摘要： 白蛋白是血清的重要组成成分，是一种高水溶性的球状蛋白质，可以维持血浆胶体渗透压平衡，兼具抗凝和抗氧化作用。血清白蛋白（serum albumin，SA）的化学结构和构象允许其与许多药物结合，影响药物的转运和代谢过程。作为内源性和外源性配体的载体蛋白，SA对于多种疾病的治疗具有重要的临床意义，包括失血性休克、低白蛋白血症、慢性肝病等。同时，SA还可以作为细胞培养剂，影响卵母细胞的体外成熟和冷冻精子的活性，在动物生产中发挥重要作用。因此，SA的需求在世界范围内逐年增加，获得高纯度、高活性、高回收率的SA至关重要。目前，SA的纯化工艺包括冷乙醇提取法、亲和沉淀、三氯乙酸/丙酮沉淀法、硫酸铵沉淀结合液相色谱法、Cohn法结合液相色谱法、色谱法。作者综述了SA的结构、生理功能、应用及纯化工艺研究进展，并总结不同纯化工艺的原理、纯化效果及优缺点，明晰SA的提取及纯化工艺进程，以期为SA的深入研究和开发利用提供理论依据，进一步推动SA在医药、分子生物学研究、免疫诊断等领域的应用。

关键词: 血清白蛋白; 功能; 应用; 纯化工艺

Abstract: Albumin is an important component of serum.It is a highly water-soluble globular protein, which can maintain the balance of colloid osmotic pressure and has both anticoagulant and antioxidant effect.Serum albumin (SA) chemical structure and conformation allows interaction with many different drugs, affecting drugs transport and metabolic processes.As a protein carrier for endogenous and exogenous ligands, SA is of great clinical significance to be used to treat a variety of diseases, including hemorrhagic shock, hypoalbuminemia, chronic liver disease, etc.At the same time, it plays an important role in animal production by acting as cell culture agent, influencing the in vitro maturation of oocytes and the viability of frozen sperm.Therefore, the demand for SA increased annually worldwide, and it is crucial to obtain SA with high purity, high activity and high recovery.Currently, the purification process of SA includes ethyl alcohol precipitation, affinity precipitation, trichloroacetic acid/acetone precipitation method, ammonium sulfate precipitation combined with liquid chromatography, Cohn method combined with liquid chromatography, and chromatography.In order to clarify the extraction and purification process of SA, the structure, physiological functions, applications and purification processes of SA were reviewed in this paper, and the principles, purification effect, advantages, disadvantages of different purification processes were summarized.It was expected to provide a reference for the in-depth research, development, and utilization of SA, and further promotes the application of SA in the fields of medicine, molecular biology research and immuno-diagnostics.

Key words: serum albumin; function; application; purification process

中图分类号:

Q512⁺.1

吴旋, 曾申明. 血清白蛋白的功能、应用及纯化工艺研究进展[J]. 中国畜牧兽医, 2023, 50(6): 2265-2275.

WU Xuan, ZENG Shenming. Research Progress on the Function,Application and Purification Technology in Serum Albumin[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2265-2275.

参考文献

[1] ROSENOER V M, ORATZ M, ROTHSCHILD M A.Albumin:Structure, Function and Uses[M].Amsterdam:Elsevier, 2014.
[2] SPADA A, EMAMI J, TUSZYNSKI J A, et al.The uniqueness of albumin as a carrier in nanodrug delivery[J].Molecular Pharmaceutics, 2021, 18(5):1862-1894.
[3] LARSEN M T, KUHLMANN M, HVAM M L, et al.Albumin-based drug delivery:Harnessing nature to cure disease[J].Molecular and Cellular Therapies, 2016, 4:3.
[4] KOUCHAKZADEH H, SAFAVI M S, SHOJAOSADATI S A.Efficient delivery of therapeutic agents by using targeted albumin nanoparticles[J].Protein and Peptide Nanoparticles for Drug Delivery, 2015, 98:121-143.
[5] KARIMI M, BAHRAMI S, RAVARI S B, et al.Albumin nanostructures as advanced drug delivery systems[J].Expert Opinion on Drug Delivery, 2016, 13(11):1609-1623.
[6] VALOJERDI F M, FARASAT A, SHARIATIFAR H, et al.Study of HSA interactions with arachidonic acid using spectroscopic methods revealing molecular dynamics of HSA-AA interactions[J].Biomedical Reports, 2020, 12(3):125-133.
[7] GANDHI S, ROY I.Synthesis and characterization of manganese ferrite nanoparticles, and its interaction with bovine serum albumin:A spectroscopic and molecular docking approach[J].Journal of Molecular Liquids, 2019, 296:111871.
[8] CHRUSZCZ M, MIKOLAJCZAK K, MANK N, et al.Serum albumins-Unusual allergens[J].Biochimica et Biophysica Acta (BBA)-General Subjects, 2013, 1830(12):5375-5381.
[9] PHAN H T, BARTELT-HUNT S, RODENHAUSEN K B, et al.Investigation of bovine serum albumin (BSA) attachment onto self-assembled monolayers (SAMs) using combinatorial quartz crystal microbalance with dissipation (QCM-D) and spectroscopic ellipsometry (SE)[J].PLoS One, 2015, 10(10):e0141282.
[10] KRENZEL E S, CHEN Z, HAMILTON J A.Correspondence of fatty acid and drug binding sites on human serum albumin:A two-dimensional nuclear magnetic resonance study[J].Biochemistry, 2013, 52(9):1559-1567.
[11] GINOSYAN S, GRABSKI H, TIRATSUYAN S.In vitro and in silico identification of the mechanism of interaction of antimalarial drug-artemisinin with human serum albumin and genomic DNA[J].bioRxiv, 2019, 20:18.
[12] CHEN R, JIANG H, PU H.Interaction of artemisinin and its derivatives with human serum albumin studied using spectroscopies and molecular modeling methods[J].Molecular Biology Reports, 2013, 40(8):4791-4804.
[13] GHUMAN J, ZUNSZAIN P A, PETITPAS I, et al.Structural basis of the drug-binding specificity of human serum albumin[J].Journal of Molecular Biology, 2005, 353(1):38-52.
[14] YANG H, LIU J, HUANG Y, et al.Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques[J].Scientific Reports, 2017, 7:45514.
[15] SPINELLA R, SAWHNEY R, JALAN R.Albumin in chronic liver disease:Structure, functions and therapeutic implications[J].Hepatology International, 2016, 10(1):124-132.
[16] CHIEN S C, CHEN C Y, LIN C F, et al.Critical appraisal of the role of serum albumin in cardiovascular disease[J].Biomarker Research, 2017, 5:31.
[17] MORISSETTE M.Colloid osmotic pressure:Its measurement and clinical value[J].Canadian Medical Association Journal, 1977, 116(8):897.
[18] GBUREK J, KONOPSKA B, GOŁB K.Renal handling of albumin-From early findings to current concepts[J].International Journal of Molecular Sciences, 2021, 22(11):5809.
[19] ROCHE M, RONDEAU P, SINGH N R, et al.The antioxidant properties of serum albumin[J].FEBS Letters, 2008, 582(13):1783-1787.
[20] BELINSKAIA D, VORONINA P, GONCHAROV N.Integrative role of albumin:Evolutionary, biochemical and pathophysiological aspects[J].Journal of Evolutionary Biochemistry and Physiology, 2021, 57(6):1419-1448.
[21] LANG J D, FIGUEROA M, CHUMLEY P, et al.Albumin and hydroxyethyl starch modulate oxidative inflammatory injury to vascular endothelium[J].The Journal of the American Society of Anesthesiologists, 2004, 100(1):51-58.
[22] GRYZUNOV Y, ARROYO A, VIGNE J L, et al.Binding of fatty acids facilitates oxidation of cysteine-34 and converts copper-albumin complexes from antioxidants to prooxidants[J].Archives of Biochemistry and Biophysics, 2003, 413(1):53-66.
[23] DATTENA M, MARA L, BIN T A A, et al.Lambing rate using vitrified blastocysts is improved by culture with BSA and hyaluronan[J].Molecular Reproduction and Development:Incorporating Gamete Research, 2007, 74(1):42-47.
[24] MENDEZ C M, MCCLAIN C J, MARSANO L S.Albumin therapy in clinical practice[J].Nutrition in Clinical Practice, 2005, 20(3):314-320.
[25] SORT P, NAVASA M, ARROYO V, et al.Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis[J].The New England Journal of Medicine, 1999, 341:403-409.
[26] POLLI F, GATTINONI L.Balancing volume resuscitation and ascites management in cirrhosis[J].Current Opinion in Anesthesiology, 2010, 23(2):151-158.
[27] CABRALES P, TSAI A G, ANANDA K, et al.Volume resuscitation from hemorrhagic shock with albumin and hexaPEGylated human serum albumin[J].Resuscitation, 2008, 79(1):139-146.
[28] SCHRIER R W.Fluid administration in critically ill patients with acute kidney injury[J].Clinical Journal of the American Society of Nephrology, 2010, 5(4):733-739.
[29] BUNN F, TRIVEDI D.Colloid solutions for fluid resuscitation[J].Cochrane Database of Systematic Reviews, 2012, 7:CD001319.
[30] VERCUEIL A, GROCOTT M P, MYTHEN M G.Physiology, pharmacology, and rationale for colloid administration for the maintenance of effective hemodynamic stability in critically ill patients[J].Transfusion Medicine Reviews, 2005, 19(2):93-109.
[31] HAYNES G, NAVICKIS R, WILKES M.Albumin administration-What is the evidence of clinical benefit? A systematic review of randomized controlled trials[J].European Journal of Anaesthesiology, 2003, 20(10):771-793.
[32] JAKUBOWSKI H.New method for the determination of protein N-linked homocysteine[J].Analytical Biochemistry, 2008, 380(2):257-261.
[33] WIEDERMANN C J.Use of hyperoncotic human albumin solution in severe traumatic brain injury revisited-A narrative review and meta-analysis[J].Journal of Clinical Medicine, 2022, 11(9):2662.
[34] JACOB M, CHAPPELL D, CONZEN P, et al.Small-volume resuscitation with hyperoncotic albumin:A systematic review of randomized clinical trials[J].Critical Care, 2008, 12(2):R34.
[35] QUINLAN G J, MARTIN G S, EVANS T W.Albumin:Biochemical properties and therapeutic potential[J].Hepatology, 2005, 41(6):1211-1219.
[36] INVESTIGATORS S S.Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units:Analysis of data from the saline versus albumin fluid evaluation (SAFE) study[J].British Medical Journal, 2006, 333(7577):1044.
[37] HALLER C.Hypoalbuminemia in renal failure:Pathogenesis and therapeutic considerations[J].Kidney and Blood Pressure Research, 2005, 28(5-6):307-310.
[38] HEDIN A, HAHN R G.Volume expansion and plasma protein clearance during intravenous infusion of 5% albumin and autologous plasma[J].Clinical Science, 2005, 108(3):217-224.
[39] GREISSMAN A, SILVER P, NIMKOFF L, et al.Albumin bolus administration versus continuous infusion in critically ill hypoalbuminemic pediatric patients[J].Intensive Care Medicine, 1996, 22(5):495-499.
[40] ZHANG L, YU W, ZHAO Y, et al.Albumin infusion may improve the prognosis of critical COVID-19 patients with hypoalbuminemia in the intensive care unit:A retrospective cohort study[J].Infection and Drug Resistance, 2022, 15:6039-6050.
[41] VIGANÓ F, PERISSINOTTO L, BOSCO V R.Administration of 5% human serum albumin in critically ill small[J].Journal of Veterinary Emergency and Critical Care, 2010, 20(2):237-243.
[42] 罗银义, 武鑫培, 徐辉, 等.胆总管结石术后低白蛋白血症患者静注外源性人血白蛋白效果评价[J].山东医药, 2022, 62(20):77-80. LUO Y Y, WU X P, XU H, et al.Evaluation of the effect of developing the use of exogenous human albumin by sedation in patients with hypoalbuminemia after choledocholithotomy[J].Shandong Medical Journal, 2022, 62(20):77-80.(in Chinese)
[43] FANALI G, DI MASI A, TREZZA V, et al.Human serum albumin:From bench to bedside[J].Molecular Aspects of Medicine, 2012, 33(3):209-290.
[44] CURTIS L, BURFORD J H, THOMAS J S M, et al.Prospective study of the primary evaluation of 1016 horses with clinical signs of abdominal pain by veterinary practitioners, and the differentiation of critical and non-critical cases[J].Acta Veterinaria Scandinavica, 2015, 57:69.
[45] BELLI C B, TÁVORA J P F, DE AZEVEDO FERREIRA R, et al.Evaluation of equine albumin solution in fluid therapy in horses with colic[J].Journal of Equine Veterinary Science, 2013, 33(7):509-514.
[46] ZHAO H, DONG Y, ZHANG Y, et al.Supplementation of SDF1 during pig oocyte in vitro maturation improves subsequent embryo development[J].Molecules, 2022, 27(20):6830.
[47] KANG J T, KWON D K, PARK S J, et al.Quercetin improves the in vitro development of porcine oocytes by decreasing reactive oxygen species levels[J].Journal of Veterinary Science, 2013, 14(1):15-20.
[48] ŞEN U, ŞIRIN E, ÖNDER H, et al.Macromolecules influence cellular competence and expression level of IGFs genes in bovine oocytes in vitro[J].Animals, 2022, 12(19):2604.
[49] 李晓霞, 曹平华, 邓星, 等.不同浓度的牛血清及牛血清白蛋白对水牛卵母细胞体外成熟的影响[J].河南农业科学, 2008, 7:108-110. LI X X, CAO P H, DENG X, et al.In vitro maturation of buffalo oocytes with different concentrations of bovine serum or BSA[J].Journal of Henan Agricultural Sciences, 2008, 7:108-110.(in Chinese)
[50] CUI X S, JIN Y X, SHEN X H, et al.Epidermal growth factor enhances meiotic resumption of canine oocytes in the presence of BSA[J].Theriogenology, 2006, 66(2):267-274.
[51] WATSON P F.The causes of reduced fertility with cryopreserved semen[J].Animal Reproduction Science, 2000, 60:481-492.
[52] TABUCHI T, SHIDARA O, HARAYAMA H.A 32-kDa tyrosine-phosphorylated protein shows a protease-dependent increase in dead boar spermatozoa[J].Journal of Reproduction and Development, 2008, 54(6):502-507.
[53] JEONG Y J, KIM M K, SONG H J, et al.Effect of α-tocopherol supplementation during boar semen cryopreservation on sperm characteristics and expression of apoptosis related genes[J].Cryobiology, 2009, 58(2):181-189.
[54] CHAVES B R, PINOTI PAVANELI A P, BLANCO-PRIETO O, et al.Exogenous albumin is crucial for pig sperm to elicit in vitro capacitation whereas bicarbonate only modulates its efficiency[J].Biology, 2021, 10(11):1105.
[55] SHALIUTINA-KOLEŠOVÁ A, DIETRICH M, XIAN M, et al.Seminal plasma transferrin effects on cryopreserved common carp Cyprinus carpio sperm and comparison with bovine serum albumin and antifreeze proteins[J].Animal Reproduction Science, 2019, 204:125-130.
[56] ROASA L, CHOI Y, LOVE C, et al.Ejaculate and type of freezing extender affect rates of fertilization of horse oocytes in vitro[J].Theriogenology, 2007, 68(4):560-566.
[57] HIDALGO M, DIAZ-JIMENEZ M, CONSUEGRA C, et al.Vitrification of donkey sperm:Is it better using permeable cryoprotectants?[J].Animals, 2020, 10(9):1462.
[58] TAKEO T, NAKAO S, MIKODA N, et al.Optimized protocols for sperm cryopreservation and in vitro fertilization in the rat[J].Laboratory Animals, 2022, 51(10):256-274.
[59] 赵娟, 李建栋.稀释液中添加精氨酸和牛血清白蛋白对驴冻精品质的影响研究[J].黑龙江畜牧兽医, 2022, 18:68-72. ZHAO J, LI J D.Effect of arginine and bovine serum albumin added to the diluent on the quality of donkey frozen semen[J].Heilongjiang Animal Science and Veterinary Medicine, 2022, 18:68-72.(in Chinese)
[60] GRIVENNIKOV S I, KARIN M.Inflammation and oncogenesis:A vicious connection[J].Current Opinion in Genetics & Development, 2010, 20(1):65-71.
[61] ODUNUGE O O, SHAZHKO A.Ammonium sulfate precipitation combined with liquid chromatography is sufficient for purification of bovine serum albumin that is suitable for most routine laboratory applications[J].Faculty Publications, 2013, doi:10.7243/2052-9341-1-3.
[62] JOHNSTON A, ADCOCK W.The use of chromatography to manufacture purer and safer plasma products[J].Biotechnology and Genetic Engineering Reviews, 2000, 17(1):37-70.
[63] TANAKA K, SHIGUEOKA E, SAWATANI E, et al.Purification of human albumin by the combination of the method of Cohn with liquid chromatography[J].Brazilian Journal of Medical and Biological Research, 1998, 31:1383-1388.
[64] DING Z, CAO X.Affinity precipitation of human serum albumin using a thermo-response polymer with an L-thyroxin ligand[J].BMC Biotechnology, 2013, 13:109.
[65] ECHAN L A, TANG H Y, ALI-KHAN N, et al.Depletion of multiple high-abundance proteins improves protein profiling capacities of human serum and plasma[J].Proteomics, 2005, 5(13):3292-3303.
[66] CHEN Y Y, LIN S Y, YEH Y Y, et al.A modified protein precipitation procedure for efficient removal of albumin from serum[J].Electrophoresis, 2005, 26(11):2117-2127.
[67] RAOUFINIA R, MOTA A, KEYHANVAR N, et al.Overview of albumin and its purification methods[J].Advanced Pharmaceutical Bulletin, 2016, 6(4):495.
[68] 翟学萍, 齐建平, 尤慧艳.模拟移动床色谱技术研究进展[J].化学教育, 2018, 39(4):1-9. ZHAI X P, QI J P, YOU H Y.Recent advances in simulated moving bed chromatography[J].Chinese Journal of Chemical Education, 2018, 39(4):1-9.(in Chinese)
[69] LU W, WANG S, LIU R, et al.Human serum albumin-imprinted polymers with high capacity and selectivity for abundant protein depletion[J].Acta Biomaterialia, 2021, 126:249-258.
[70] WULAN D R, RAHMANIYAH W R, ZULFIKAR M A, et al.Enhancement of microsphere specificity to purify human serum albumin from blood plasma[J].Journal of Chromatography A, 2022, 1683:463535.