【摘要】：全球越來越多的人受到心腦血管疾病的侵害,心腦血管疾病的病發(fā)主要是在不同情況下血小板的聚集形成血栓而導(dǎo)致的。目前為止我們只能借助醫(yī)療器械的前期診斷和手術(shù)介入來治療該疾病。而對于與血液接觸的醫(yī)療器械,我們必須保證其有良好的生物相容性,從而在生理環(huán)境下不會導(dǎo)致發(fā)生血栓性凝血。316L醫(yī)用不銹鋼是一種在醫(yī)療器械領(lǐng)域應(yīng)用廣泛的醫(yī)用金屬材料,可用于人工關(guān)節(jié)、人工骨等,但由于其表面活性基團(tuán)少、親水性差等因素導(dǎo)致其抗凝血性不夠理想,需對材料做必要的表面改性。表面共價接枝法因?yàn)槠涓男缘男Ч�(wěn)定,表面修飾時不損害材料自身性能等優(yōu)點(diǎn)己成為表面改性的常用方法。本課題設(shè)計(jì)通過在316L醫(yī)用不銹鋼表面接枝抗凝劑分子,進(jìn)而提高其抗凝血性。主要工作如下： 首先高通量下載發(fā)表在NCBI數(shù)據(jù)庫中各種抗凝血多肽序列進(jìn)行篩選,將篩選后的序列用CLUSTAL軟件進(jìn)行多序列比對,找出抗凝血多肽的保守序列。再從保守序列出發(fā),通過Discovery Studio軟件進(jìn)行同源建模以預(yù)測其三級結(jié)構(gòu)；并用分子對接軟件模擬篩選的抗凝劑與凝血酶分子進(jìn)行對接,來驗(yàn)證其與凝血酶的結(jié)合效果并進(jìn)行相關(guān)分析。 隨后利用等離子體處理316L醫(yī)用不銹鋼表面,將烯丙胺沉積在其表面形成氨基薄膜。通過對SS-PPAa的表面表征(水接觸角、XPS)和氨基定量檢測表明SS-PPAa表面的水接觸角顯著降低且平均氨基密度達(dá)到39.8nmol/cm2,為藥物的表面接枝提供了充分的結(jié)合位點(diǎn)。 用碳二亞胺(EDC)和戊二醛(GTA)法將五種抗凝劑(AG、BV、抗凝劑A和B, fPRPG)固定在SS-PPAa表面,對改性后的材料進(jìn)行表面表征(水接觸角、XPS)和體外抗凝血性評價(親水性、血小板粘附和APTT,PT),發(fā)現(xiàn)五種抗凝劑均不同程度接枝到316L醫(yī)用不銹鋼表面。綜上所述,本課題對于316L不銹鋼表面的抗凝血修飾和抗凝血評價做了初步的探究：阿加曲班、比伐盧定、小分子五肽修飾的不銹鋼表現(xiàn)出了良好的抗凝血趨勢,抗凝劑A和B修飾后樣品抗凝血效果較一般,未達(dá)到理想的抗凝血效果；同時發(fā)現(xiàn)EDC法優(yōu)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.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R318.08

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本文編號：2143448