Ti-O膜表面固定不同手性酒石酸及其对催化释放一氧化氮与血液相容性的影响

发布时间：2018-03-26 17:13

本文选题：手性　切入点：酒石酸　出处：《西南交通大学》2017年硕士论文

【摘要】：手性是生命体系的基本特征,构成生命体的有机分子绝大多数是手性分子,并表现出高度的手性选择,因此不同的手性分子与生物体系相互作用会表现出不同的生物学功能。本论文首先通过聚多巴胺和己二胺在Ti-O膜表面构建不同的手性体系,即固定手性酒石酸体系和固定手性酒石酸钠体系,对手性体系进行筛选,随后对筛选出的手性表面进行纤维蛋白原变性和血小板粘附与激活实验评价,考察手性表面的血液相容性。硒代胱胺分子中二硒键具有催化内源性一氧化氮供体释放一氧化氮的能力,因此本论文还将硒代胱胺取代己二胺,在材料次表面引入催化活性中心,最后在材料的最表面接枝手性酒石酸,考察不同手性酒石酸的固定对次表面硒代胱胺催化供体释放一氧化氮的影响以及随后对血小板粘附与激活的影响。X射线光电子能谱(XPS)、水接触角测量(WCA)等方法对改性后的样品进行材料学的表征,结果表明沉积聚多巴胺的表面新出现N1s峰,而Ti-O膜上的Ti2p峰被完全遮盖,说明聚多巴胺薄膜制备成功。接枝己二胺样品表面的N:C比例升高是因为引入了大量的氨基,表明己二胺接枝成功,随后接枝手性酒石酸和手性酒石酸钠的样品表面O:C比例升高表明手性酒石酸和手性酒石酸钠接枝成功。WCA结果显示,在材料表面固定同一系列手性分子,水接触角几乎没有改变说明表面手性不影响材料表面的亲疏水性;利用QCM-D方法实时监测各样品对血浆蛋白如纤维蛋白原、牛血清白蛋白的吸附情况,结果直接证明样品表面接枝的L-酒石酸和D-酒石酸数量无明显差异,但随后接枝D-酒石酸的样品表面吸附纤维蛋白原量和牛血清白蛋白量显著多于接枝L-酒石酸的样品表面吸附的纤维蛋白原量和牛血清白蛋白量,固定D-酒石酸的样品对血浆蛋白显示出更好的亲和性,这表明表面手性对蛋白吸附行为有着不可忽视的影响。而对于固定L-酒石酸钠样品来说,结果同样显示固定D-酒石酸钠样品表面有利于纤维蛋白原和白蛋白的吸附,但两者吸附量的差值与表面固定酒石酸系列样品相比显著降低。尽管与固定L-酒石酸样品相比,固定D-酒石酸样品吸附纤维蛋白原量要多,但是通过纤维蛋白变性实验结果可知,固定D-酒石酸样品表面上的纤维蛋白原变性程度显著低于固定L-酒石酸样品表面的,在随后的血小板的粘附与激活实验中,固定D-酒石酸样品也表现出了更好的抗血小板粘附与激活的能力。为了更进一步研究手性对催化供体释放一氧化氮能力的影响,本论文用无手性但具有催化中心的硒代胱胺代替己二胺,硒代胱胺可以催化供体释放一氧化氮,在材料表面引入催化活性中心,将L-/D-酒石酸接枝到材料表面,在材料的表面引入手性元素。XPS的结果显示当硒代胱胺接枝到聚多巴胺样品后,材料表面新出现了 Se元素,通过材料表面各元素高分辨图谱的解析可得,接枝上不同手性酒石酸分子样品的硒元素含量约为0.5%,固定D-酒石酸样品催化内源性供体释放NO的速率为1.0×10-10mol/cm2,而固定L-酒石酸样品催化速率为0.7×10-10-10mol/cm2,说明固定D-酒石酸样品具有更优的催化内源性供体释放NO的能力。随后的血小板粘附实验结果表明,在血浆中未添加内源性一氧化氮供体的情况下,沉积聚多巴胺样品表面血小板粘附量最多,固定D-酒石酸样品血小板粘附量少于固定L-酒石酸样品的,Ti-O表面具有最优的抗血小板粘附和激活性能;在血浆中添加供体的情况下,具有催化供体释放NO的样品表面血小板粘附数量明显减少,固定D-酒石酸样品表面粘附的血小板数量最少,显著低于表面固定L-酒石酸样品和表面仅固定硒代胱氨样品。
[Abstract]:Chirality is a basic feature of life system, constitute the organic molecules for life the vast majority of chiral molecules, and showed high chiral, chiral molecules and biological systems in different interactions will exhibit different biological functions. This paper firstly by poly dopamine and hexanediamine system in different construction of chiral Ti-O film the surface is fixed, the chiral tartaric acid system and fixed chiral sodium tartrate system, chiral system for screening, then the chiral surface were screened and fibrinogen denaturation and platelet adhesion and activation of experimental evaluation, study the chiral surface blood compatibility. Two se bond selenocystamine molecule with catalytic ability of endogenous nitric oxide the release of nitric oxide donor, so this paper will also replace selenocystamine 1,6-diaminohexane, in material surface into the catalytic center, finally in the material most Surface grafting chiral tartaric acid, the effect of different chiral tartaric acid fixation on surface selenocystamine and subsequent release of nitric oxide donor catalytic effect on platelet adhesion and activation of.X ray photoelectron spectroscopy (XPS), water contact angle measurement (WCA) method for characterization of materials science of modified samples the results show that the surface deposition, polydopamine new N1s peak, and Ti-O on the membrane of Ti2p peak was completely covered, that the polydopamine films were prepared on the surface of the sample. The grafting ratio of N:C increased, because of the introduction of a large number of amino grafting showed that hexanediamine successfully, then grafted chiral tartaric acid and chiral tartaric acid sodium the sample surface increased the proportion of O:C showed that the chiral tartaric acid and chiral sodium tartrate grafted.WCA showed that the surface of the material is fixed with a series of chiral molecules, the water contact angle has little change that The surface does not affect the hydrophobicity of chiral material surface; on plasma proteins such as fibrinogen by QCM-D method for real-time monitoring of each sample, the adsorption of bovine serum albumin, the direct evidence that no significant difference between the number of L- tartaric acid and D- acid tartrate grafted sample surface, but the amount of fibrinogen and bovine serum albumin was then the adsorption of tartaric acid grafted D- sample surface fibrinogen content and bovine serum albumin was significantly more than the grafted L- tartaric acid adsorbed on the surface of the sample, the fixed D- tartaric acid on plasma protein samples showed better affinity, suggesting that the chiral surface has a negligible effect on the protein adsorption behavior for a fixed. L- sodium tartrate samples, results also showed that the immobilized D- sodium tartrate sample surface to fibrinogen and albumin adsorption, but the difference between the adsorption capacity and surface fixed Tartaric acid series samples compared to the significantly reduced. Compared with the fixed L- tartaric acid samples, fixed D- tartaric acid sample adsorption amount to the original fiber protein, but the experimental results showed that fiber protein denaturation, fixed D- tartaric acid samples on the surface of the fibrinogen denaturation degree was significantly lower than that of the fixed L- tartaric acid on the surface of the sample, in then the adhesion and activation of platelets in the experiment, the fixed D- tartaric acid samples also showed better anti platelet adhesion and activation ability. In order to further study on the chiral catalytic ability to influence the release of nitric oxide donor, this paper used selenocystamine achiral but has the catalytic center instead of 1,6-diaminohexane, selenocystamine the donor can catalyze the release of nitric oxide, in the catalytic center into material surface, L-/D- tartaric acid was grafted onto the surface of the material, the introduction of chiral.XPS elements on the surface of the material. The results show that when selenocystamine grafted onto the polydopamine samples, the new material surface appeared Se elements, each element of material surface through high resolution map analysis can be grafted, selenium content of different chiral tartaric acid molecular sample is about 0.5%, fixed rate D- tartaric acid catalyzed endogenous release of NO donor samples for 1 x 10-10mol/cm2, fixed L- tartaric acid sample catalytic rate is 0.7 * 10-10-10mol/cm2, the fixed D- tartaric acid sample has better catalytic ability of endogenous release of NO. The donor platelet adhesion following experimental results show that in the plasma without endogenous nitric oxide donor under the condition of polydopamine deposition surface of platelet adhesion amount most fixed D- tartaric acid samples of platelet adhesion less than fixed L- tartaric acid samples, platelet adhesion and activation of the Ti-O surface has the best performance in plasma; In addition, the number of platelets adhered to the surface of the sample with NO released by the donor decreased significantly. The number of platelets adhered on the fixed D- tartaric acid sample was the least, which was significantly lower than that of the surface fixed L- tartaric acid sample and the surface only fixed selenocysteine sample.

【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O643.36

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