小分子多肽抗凝剂的筛选及改性医用不锈钢材料
发布时间：2018-07-25 09:59
【摘要】：全球越来越多的人受到心脑血管疾病的侵害,心脑血管疾病的病发主要是在不同情况下血小板的聚集形成血栓而导致的。目前为止我们只能借助医疗器械的前期诊断和手术介入来治疗该疾病。而对于与血液接触的医疗器械,我们必须保证其有良好的生物相容性,从而在生理环境下不会导致发生血栓性凝血。316L医用不锈钢是一种在医疗器械领域应用广泛的医用金属材料,可用于人工关节、人工骨等,但由于其表面活性基团少、亲水性差等因素导致其抗凝血性不够理想,需对材料做必要的表面改性。表面共价接枝法因为其改性的效果稳定,表面修饰时不损害材料自身性能等优点己成为表面改性的常用方法。本课题设计通过在316L医用不锈钢表面接枝抗凝剂分子,进而提高其抗凝血性。主要工作如下： 首先高通量下载发表在NCBI数据库中各种抗凝血多肽序列进行筛选,将筛选后的序列用CLUSTAL软件进行多序列比对,找出抗凝血多肽的保守序列。再从保守序列出发,通过Discovery Studio软件进行同源建模以预测其三级结构；并用分子对接软件模拟筛选的抗凝剂与凝血酶分子进行对接,来验证其与凝血酶的结合效果并进行相关分析。 随后利用等离子体处理316L医用不锈钢表面,将烯丙胺沉积在其表面形成氨基薄膜。通过对SS-PPAa的表面表征(水接触角、XPS)和氨基定量检测表明SS-PPAa表面的水接触角显著降低且平均氨基密度达到39.8nmol/cm2,为药物的表面接枝提供了充分的结合位点。 用碳二亚胺(EDC)和戊二醛(GTA)法将五种抗凝剂(AG、BV、抗凝剂A和B, fPRPG)固定在SS-PPAa表面,对改性后的材料进行表面表征(水接触角、XPS)和体外抗凝血性评价(亲水性、血小板粘附和APTT,PT),发现五种抗凝剂均不同程度接枝到316L医用不锈钢表面。综上所述,本课题对于316L不锈钢表面的抗凝血修饰和抗凝血评价做了初步的探究：阿加曲班、比伐卢定、小分子五肽修饰的不锈钢表现出了良好的抗凝血趋势,抗凝剂A和B修饰后样品抗凝血效果较一般,未达到理想的抗凝血效果；同时发现EDC法优于戊二醛接枝法的抗凝效果；
[Abstract]:More and more people around the world are affected by cardiovascular and cerebrovascular diseases, which are mainly caused by platelet aggregation and thrombosis under different conditions. So far, we can only treat the disease with early diagnosis and surgical intervention of medical devices. And for medical devices that come into contact with blood, we have to make sure that they have good biocompatibility, Therefore, in physiological environment, thrombotic coagulation. 316L medical stainless steel is a kind of medical metal material widely used in the field of medical instruments, which can be used in artificial joints, artificial bones, etc., but its surface active groups are few. Due to the poor hydrophilicity and other factors, the anticoagulant is not ideal, so the necessary surface modification of the material is needed. Surface covalent grafting has become a common method for surface modification because of its stable effect and the advantages of surface modification without damaging the properties of the material itself. In this paper, anticoagulant molecules were grafted on 316L medical stainless steel surface to improve anticoagulability. The main work is as follows: firstly, various anticoagulant polypeptide sequences were screened by high-throughput download and published in NCBI database. The selected sequences were compared with CLUSTAL software to find the conserved sequences of anticoagulant peptides. Based on the conserved sequence, the homology modeling was carried out by Discovery Studio software to predict its tertiary structure, and the anticoagulant screened by molecular docking software was used for docking with thrombin molecule. To verify its binding effect with thrombin and to carry out correlation analysis. Then the surface of 316L medical stainless steel was treated by plasma and the allylamine was deposited on the surface to form an amino film. The surface characterization of SS-PPAa (water contact angle) and the quantitative analysis of amino groups showed that the water contact angle of SS-PPAa surface decreased significantly and the average amino density reached 39.8 nmol / cm ~ 2, which provided sufficient binding sites for the surface grafting of SS-PPAa. Five anticoagulants A and B, fPRPG) were immobilized on the surface of SS-PPAa by carbodiimide (EDC) and glutaraldehyde (GTA) method. The modified materials were characterized by water contact angle (GTA) and anticoagulant evaluation in vitro (hydrophilicity). Platelet adhesion and APTT PT), it was found that the five anticoagulants were grafted to 316L medical stainless steel surface to varying degrees. To sum up, this paper makes a preliminary study on the anticoagulant modification and anticoagulant evaluation of 316L stainless steel surface: Agatreban, Bivaludine, small molecular pentapeptide modified stainless steel showed a good anticoagulant trend. The anticoagulant effect of anticoagulant A and B was not satisfactory, and the anticoagulant effect of EDC was better than that of glutaraldehyde grafting.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R318.08
本文编号：2143448
[Abstract]:More and more people around the world are affected by cardiovascular and cerebrovascular diseases, which are mainly caused by platelet aggregation and thrombosis under different conditions. So far, we can only treat the disease with early diagnosis and surgical intervention of medical devices. And for medical devices that come into contact with blood, we have to make sure that they have good biocompatibility, Therefore, in physiological environment, thrombotic coagulation. 316L medical stainless steel is a kind of medical metal material widely used in the field of medical instruments, which can be used in artificial joints, artificial bones, etc., but its surface active groups are few. Due to the poor hydrophilicity and other factors, the anticoagulant is not ideal, so the necessary surface modification of the material is needed. Surface covalent grafting has become a common method for surface modification because of its stable effect and the advantages of surface modification without damaging the properties of the material itself. In this paper, anticoagulant molecules were grafted on 316L medical stainless steel surface to improve anticoagulability. The main work is as follows: firstly, various anticoagulant polypeptide sequences were screened by high-throughput download and published in NCBI database. The selected sequences were compared with CLUSTAL software to find the conserved sequences of anticoagulant peptides. Based on the conserved sequence, the homology modeling was carried out by Discovery Studio software to predict its tertiary structure, and the anticoagulant screened by molecular docking software was used for docking with thrombin molecule. To verify its binding effect with thrombin and to carry out correlation analysis. Then the surface of 316L medical stainless steel was treated by plasma and the allylamine was deposited on the surface to form an amino film. The surface characterization of SS-PPAa (water contact angle) and the quantitative analysis of amino groups showed that the water contact angle of SS-PPAa surface decreased significantly and the average amino density reached 39.8 nmol / cm ~ 2, which provided sufficient binding sites for the surface grafting of SS-PPAa. Five anticoagulants A and B, fPRPG) were immobilized on the surface of SS-PPAa by carbodiimide (EDC) and glutaraldehyde (GTA) method. The modified materials were characterized by water contact angle (GTA) and anticoagulant evaluation in vitro (hydrophilicity). Platelet adhesion and APTT PT), it was found that the five anticoagulants were grafted to 316L medical stainless steel surface to varying degrees. To sum up, this paper makes a preliminary study on the anticoagulant modification and anticoagulant evaluation of 316L stainless steel surface: Agatreban, Bivaludine, small molecular pentapeptide modified stainless steel showed a good anticoagulant trend. The anticoagulant effect of anticoagulant A and B was not satisfactory, and the anticoagulant effect of EDC was better than that of glutaraldehyde grafting.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R318.08
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