杜振兴,周斯仪,钟赛意,黄凤娇,陈观兰,陈菁,洪鹏志,章超桦

• 1:广东海洋大学食品科技学院
• 2:广东海洋大学深圳研究院
• 3:广东省水产品加工与安全重点实验室

摘要(Abstract)：

【目的】为海洋生物源肝素的研究提供参考依据,促进海洋生物资源的综合利用。【方法】对海洋生物源肝素的提取技术、分离纯化技术、结构鉴定、生物活性进行了归纳总结。【结果】海洋生物源肝素作为传统肝素的替代原料,具有副作用小、与人体细胞兼容性好的特点,但其提取率不如陆地生物源肝素高,且对其活性机制的研究还不够透彻,未能掌握肝素特异结构与活性间的关系。【结论】为充分开发海洋生物源肝素,未来的研究重点应该包括改进海洋生物源肝素的制备和合成、开发改进性能的肝素抗凝剂、开发新的生物活性以及相应的药物或保健品、更新肝素原料库。

关键词(KeyWords)： 肝素;海洋生物;分离纯化;结构分析;生物活性

Abstract:

Keywords:

基金项目(Foundation): 广东省渔港建设和渔业产业发展专项资金(A201708C13));; 深圳市科技计划项目(JCYJ20170818111335796);; 湛江市海洋经济创新发展示范市建设项目(湛海创2017C8B1);; 广东普通高等学校水产品高值化加工与利用创新团队项目(GDOU2016030503)

作者(Author): 杜振兴,周斯仪,钟赛意,黄凤娇,陈观兰,陈菁,洪鹏志,章超桦

参考文献(References)：

• [1]凌沛学,何兆雄,姬胜利.肝素[M].北京:中国轻工业出版社,2015:45.
• [2]XIE X,RIVIER A S,ZAKRZEWICZ A,et al.Inhibition of selectin-mediated cell adhesion and prevention of acute inflammation by nonanticoagulant sulfated saccharides studies with carboxyl-reduced and sulfated heparin and with trestatin a sulfate[J].Journal of Biological Chemistry,2000,275(44):34818-34825.
• [3]COLLIEC-JOUAULT S,BAVINGTON C,DELBARRELADRAT C.Heparin-like entities from marine organisms[M]//Heparin-A Century of Progress.Berlin:Springer,2012:423-449.
• [4]DREYFUSS J L,REGATIERI C V,LIMA M A,et al.A heparin mimetic isolated from a marine shrimp suppresses neovascularization[J].Journal of Thrombosis and Haemostasis,2010,8(8):1828-1837.
• [5]ANDRADE G P V,LIMA M A,DE SOUZA JUNIOR A A,et al.A heparin-like compound isolated from a marine crab rich in glucuronic acid 2-O-sulfate presents low anticoagulant activity[J].Carbohydrate polymers,2013,94(1):647-654.
• [6]JESKE W P,MCDONALD M K,HOPPENSTEADT D A,et al.Isolation and characterization of heparin from tuna skins[J].Clinical and Applied Thrombosis/Hemostasis,2007,13(2):137-145.
• [7]ARUMUGAM M,GARG H,AJITHKUMAR T,et al.Antiproliferative heparin(glycosaminoglycans)isolated from giant clam(Tridacna maxima)and green mussel(Perna viridis)[J].African journal of biotechnology,2009,8(10):2394-2396.
• [8]CAO J L,WEN C R,LU J J,et al.Characterization of acidic polysaccharides from the mollusks through acid hydrolysis[J].Carbohydrate polymers,2015,130:268-274.
• [9]SEEDEVI P,MOOVENDHAN M,VAIRAMANI S,et al.Mucopolysaccharide from cuttlefish:Purification,chemical characterization and bioactive potential[J].Carbohydrate Polymers,2017,167:129-135.
• [10]陈思,张小军,龙举,等.海洋生物中肝素类物质的提取纯化技术研究进展[J].安徽农业科学,2015,43(32):82-84.
• [11]FIDELIS G P,CAMARA R B G,QUEIROZ M F,et al.Proteolysis,Na OH and ultrasound-enhanced extraction of anticoagulant and antioxidant sulfated polysaccharides from the edible seaweed,Gracilaria birdiae[J].Molecules,2014,19(11):18511-18526.
• [12]王国栋,杨佳艺,杨佳,等.肝素提取纯化技术研究进展[J].食品工业科技,2012,33(9):436-440.
• [13]刘斌,鲁娇娇,艾春青,等.LC-MS技术分析5种贝类中的含糖醛酸多糖[C]//中国食品科学技术学会第十三届年会论文摘要集.北京:中国食品科学技术学会,2016:238-239.
• [14]TICAR B F,ROHMAH Z,AMBUT C V,et al.Enzyme-assisted extraction of anticoagulant polysaccharide from Liparis tessellatus eggs[J].International journal of biological macromolecules,2015,74:601-607.
• [15]LUPPI E,CESARETTI M,VOLPI N.Purification and characterization of heparin from the Italian clam Callista chione[J].Biomacromolecules,2005,6(3):1672-1678.
• [15]DIETRICH C P,PAIVA J F,CASTRO R A B,et al.Structural features and anticoagulant activities of a novel natural low molecular weight heparin from the shrimp Penaeus brasiliensis[J].Biochimica et Biophysica Acta(BBA)-General Subjects,1999,1428(2/3):273-283.
• [16]詹雯琦,路海霞,蔡水淋,等.海洋贝类中糖胺聚糖研究进展[J].渔业研究,2016,38(1):73-80.
• [17]孙晓明.四角蛤蜊糖胺聚糖提取?纯化及生理活性研究[D].天津:天津科技大学,2011:37-44.
• [18]SARAVANAN R,SHANMUGAM A.Isolation and characterization of low molecular weight glycosaminoglycans from marine mollusc Amussium pleuronectus(Linne)using chromatography[J].Applied biochemistry and biotechnology,2010,160(3):791-799.
• [19]田亚平.生化分离技术[M].北京:化学工业出版社,2006:69-98.
• [20]刘叶青.生物分离工程实验[M].2版.北京:高等教育出版社,2014:57-62.
• [21]CHAVANTE S F,BRITO A S,LIMA M,et al.A heparin-like glycosaminoglycan from shrimp containing high levels of 3-O-sulfated D-glucosamine groups in an unusual trisaccharide sequence[J].Carbohydrate Research,2014,390:59-66.
• [22]CESARETTI M,LUPPI E,MACCARI F,et al.Isolation and characterization of a heparin with high anticoagulant activity from the clam Tapes phylippinarum:evidence for the presence of a high content of antithrombin III binding site[J].Glycobiology,2004,14(12):1275-1284.
• [23]FLENGSRUD R,LARSEN M L,?DEGAARD O R.Purification,characterization and in vivo studies of salmon heparin[J].Thrombosis Research,2010,126(6):e409-e417.
• [24]张丽芝,沈荣.单糖组成分析方法的研究进展[J].微生物学免疫学进展,2013,41(1):112.
• [25]HARAZONO A,KOBAYASHI T,KAWASAKI N,et al.A comparative study of monosaccharide composition analysis as a carbohydrate test for biopharmaceuticals[J].Biologicals,2011,39(3):171-180.
• [26]LI H Y,MAO W J,ZHANG X L,et al.Structural characterization of an anticoagulant-active sulfated polysaccharide isolated from green alga Monostroma latissimum[J].Carbohydrate Polymers,2011,85(2):394-400.
• [27]曹九零.20种海洋贝类中多糖成分的分析[D].大连:大连工业大学,2015:28-35.
• [28]史旭波,胡大一.肝素的抗凝机制及临床相关问题[J].临床荟萃,2007,22(18):1293-1295.
• [29]VOLPI N.Occurrence and structural characterization of heparin from molluscs[J].Invertebrate Survival Journal,2005,2(1):6-16.
• [30]LISMAN T,ADELMEIJER J,NIEUWENHUIS H K,et al.Enhancement of fibrinolytic potential in vitro by anticoagulant drugs targeting activated factor X,but not by those inhibiting thrombin or tissue factor[J].Blood Coagulation And Fibrinolysis,2003,14(6):557-562.
• [31]GOMES A M,KOZLOWSKI E O,POMIN V H,et al.Unique extracellular matrix heparan sulfate from the bivalve Nodipecten nodosus(Linnaeus,1758)safely inhibits arterial thrombosis after photochemically induced endothelial lesion[J].Journal of Biological Chemistry,2010,285(10):7312-7323.
• [32]孙佳凤,蒋婷婷,邱晓东,等.肝素抗炎作用的研究进展[J].东南大学学报(医学版),2014,33(6):798-802.
• [33]GOMES A M,KOZLOWSKI E O,BORSIG L,et al.Antitumor properties of a new non-anticoagulant heparin analog from the mollusk Nodipecten nodosus:Effect on P-selectin,heparanase,metastasis and cellular recruitment[J].Glycobiology,2014,25(4):386-393.
• [34]BRITO A S,ARIMATéIA D S,SOUZA L R,et al.Anti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp[J].Bioorganic&Medicinal Chemistry,2008,16(21):9588-9595.
• [35]DREYFUSS J L,REGATIERI C V,LIMA M A,et al.A heparin mimetic isolated from a marine shrimp suppresses neovascularization[J].Journal of Thrombosis and Haemostasis,2010,8(8):1828-1837.
• [36]MACCARI F,VOLPI N.Heparin from marine mollusks:occurrence,structure,and biological role[M].Marine Glycobiology.CRC Press,2016:59-68.