透明质酸锌的合成及在小鼠创面修复中的应用
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摘要
目的:对合成的透明质酸锌的理化性质进行鉴定,并观察其对小鼠创面愈合的影响。方法:取10只小鼠,雌雄各半,在小鼠左右两侧采取八针法垫圈制备皮肤全层缺损创面模型,左右两侧分别涂抹透明质酸锌溶液和透明质酸钠溶液,无菌纱布包裹伤口,每天换药1次,于手术后观察各组创面修复情况。利用钠离子检测仪检测透明质酸锌的生成;利用平板涂布法观察透明质酸锌的抑菌效果;使用元素分析法测定生成的透明质酸锌所含钠离子和锌离子含量。结果:透明质酸钠与氯化锌反应生成透明质酸锌,其中锌离子与透明质酸为共价结合;透明质酸锌溶液具有抗菌功能(P<0.05);小鼠全皮切除结果显示透明质酸锌比透明质酸钠促创面修复效果更显著(P<0.05)。结论:透明质酸与锌通过共价键结合,透析可得到纯度极高的透明质酸锌固体;透明质酸锌相比透明质酸钠促创面愈合效果更好。
Objective: To react sodium hyaluronate with zinc chloride, then identify the physicochemical properties of the zinc hyaluronate, and observed its effect on wound healing in mice. Methods: The rubber ring was sewn with eight stitches onto the skin of 10 mice, half male and half female, to make a full-thickness wound model of the skin on the left and right sides of the mice. The left and right side were respectively coated with zinc hyaluronate solution and sodium hyaluronate solution, wrapped in sterile gauze. The medicine was changed once a day, and the wound healing of each group was observed after the operation. The sodium ion detector was used to detect the formation of zinc hyaluronate, and then the antibacterial effect of zinc hyaluronate was studied using spread plate technique. Elemental analysis was made to detect the sodium and zinc ions content of zinc hyaluronate. Results: Sodium hyaluronate reacted with zinc chloride to form zinc hyaluronate, in which zinc ions were covalently bonded with hyaluronic acid. Zinc hyaluronic acid solution also had antibacterial function(P<0.05). The results of whole skin resection in mice showed that zinc hyaluronate was more effective than sodium hyaluronate to promote wound repair(P<0.05). Conclusion: Hyaluronic acid and zinc can be combined by covalent bond, and zinc hyaluronate solid with high purity can be obtained by dialysis. Zinc hyaluronate can promote wound healing better than sodium hyaluronate.
Objective: To react sodium hyaluronate with zinc chloride, then identify the physicochemical properties of the zinc hyaluronate, and observed its effect on wound healing in mice. Methods: The rubber ring was sewn with eight stitches onto the skin of 10 mice, half male and half female, to make a full-thickness wound model of the skin on the left and right sides of the mice. The left and right side were respectively coated with zinc hyaluronate solution and sodium hyaluronate solution, wrapped in sterile gauze. The medicine was changed once a day, and the wound healing of each group was observed after the operation. The sodium ion detector was used to detect the formation of zinc hyaluronate, and then the antibacterial effect of zinc hyaluronate was studied using spread plate technique. Elemental analysis was made to detect the sodium and zinc ions content of zinc hyaluronate. Results: Sodium hyaluronate reacted with zinc chloride to form zinc hyaluronate, in which zinc ions were covalently bonded with hyaluronic acid. Zinc hyaluronic acid solution also had antibacterial function(P<0.05). The results of whole skin resection in mice showed that zinc hyaluronate was more effective than sodium hyaluronate to promote wound repair(P<0.05). Conclusion: Hyaluronic acid and zinc can be combined by covalent bond, and zinc hyaluronate solid with high purity can be obtained by dialysis. Zinc hyaluronate can promote wound healing better than sodium hyaluronate.
引文
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[2]胡安根.生物活性玻璃和透明质酸钠结合修复材料治疗烧伤创面临床分析[J].亚太传统医药,2013,9(9):116-117.
[3]孙学宾.锌制剂的合理应用[J].社区医学志,2005,3(1):35-35.
[4]BURGER K,ILLéS J,GYURCSIK B,et al.Metal ion coordination of macromolecular bioligands:formation of zinc(II)complex of hyaluronic acid[J].Carbohydr Res,2001,332(2):197-207.
[5]刘阳.新型藻酸盐创面敷料及组织工程支架的开发研究[D].广州:中山大学,2007.
[6]徐媛,刘宏伟.创面修复“TIME”原则及其意义[J].中国组织工程研究,2012,16(11):2059-2062.
[6]魏先锋,张剑.生长因子和细胞外基质在创伤修复过程中的作用[J].国外医学:耳鼻咽喉科学分册,2004,28(2):100-102.
[7]柳大烈.透明质酸与创伤无瘢痕愈合[J].中国临床康复,2002,6(4):474-475.
[8]凌沛学,梁虹.透明质酸钠在关节疾病中的应用[J].中国修复重建外科杂志,2002,16(1):1-4.
[9]张娟娟,刘尊英,董士远,等.锌离子结合类蛋白反应修饰肽的稳定性研究[J].现代食品科技,2015,31(9):150-154.
[10]CAI C,LIN P,ZHU H,et al.Zinc binding to MG53 facilitates repair of injury to cell membrane[J].J Biol Chem,2015,290(22):13830-13839.
[11]项荣,丁栋博,范亮亮,等.氧化锌的抗菌机制及其安全性研究进展[J].中国组织工程研究,2014,18(3):470-475.
[12]韩芳,董许英.炉甘石洗剂联合冰片治疗II,III期压疮疗效观察[J].中国社区医师:医学专业,2011(34):187-187.
[13]BURGER K,IIIéS J,GYURCSIK B,et al.Metal ion coordination of macromolecular bioligands:formation of zinc(II)complex of hyaluronic acid[J].Carbohydr Res,2001,332(2):197-207.
[14]乔亮,杨惠忠,黄晓琴,等.使用愈肤欣?透明质酸锌凝胶在急、慢性创面愈合过程中的临床研究:中华医学会烧伤外科学分会2009年学术年会论文汇编[G].北京:中华医学会烧伤外科学分会,2009:197.
[15]匈牙利吉瑞大药厂.用于治疗多发性硬化的包含透明质酸锌的复合物的药物组合物:CN1882352[P].2006.
[16]郭仕华.玻璃酸锌的制备及其促进角膜损伤愈合的研究[D].济南:山东大学,2006.
[17]杨桂兰.透明质酸锌的制备方法和用途:中国药学会全国多糖类药物研究与应用研讨会论文集[C].北京:中国药学会生化与生物技术药物专业委员会,2008:4.