氧化低密度脂蛋白对红细胞的损伤

发布时间：2018-01-14 17:06

本文关键词：氧化低密度脂蛋白对红细胞的损伤　出处：《重庆大学》2005年硕士论文　论文类型：学位论文

【摘要】：血液流变学研究正朝着细胞水平和分子水平发展,在细胞和分子水平上更深入地研究引起红细胞力学特性变化及整个血液流变学特性变化的分子生物学机制,有助于从根本上认识红细胞变形的生理和临床意义,为许多与红细胞流变学相关的疾病的基础病理研究和临床研究提供重要的依据。生物学和医学界一般认为,低密度脂蛋白(LDL)被氧化修饰为氧化低密度脂蛋白(Ox—LDL)后, 能损伤动脉内皮细胞,损伤的动脉内皮细胞就会转化为泡沫细胞, 进而形成AS 病灶,这说明低密度脂蛋白促进AS 的发生和发展;但生物学和医学界就Ox—LDL 对红细胞的损伤了解甚少。通过大量的实验研究证明:红细胞主要的力学性质表现为红细胞膜的粘弹性,红细胞膜的粘弹性的变化与生物体内普遍存在的,膜蛋白的氧化损伤与氧自由基反应机制间存在明确的相关性,从而说明红细胞膜的氧化损伤是导致红细胞膜力学性质变化的分子生物学机制。(可能来自不同的病理或生理原因,但都产生氧自由基损伤) 在本研究工作中,检索查阅了相关的文献资料,应用了细胞流变学的基本原理和实验方法,学习了Chien 的关于红细胞膜(本构关系)“半球帽子模型”,通过该模型来研究膜蛋白氧化损伤对膜变形的动力学过程的影响;结合分子生物学的理论和生化分析方法,运用分子生物学技术,通过SDS-PAGE 电泳,表明氧化损伤的膜蛋白中出现分子量高于Spectrin的新谱带HMB,其结果将限制膜蛋白的空间构象变化和共振自由度,最终导致膜弹性系数和膜粘性系数的变化。本文系统地研究了红细胞膜蛋白的氧化损伤对红细胞膜粘弹性的影响和膜蛋白组成的改变。通过本文的研究,我们可以认为:Ox—LDL 对红细胞的损伤主要表现为红细胞膜的损伤即膜蛋白组成的改变,红细胞膜损伤后,使红细胞的变形性降低及携氧和释氧能力的下降,红细胞的变形性降低使得血液粘性增加,血流速度减慢,导致内皮细胞受损;红细胞变形性减退意味着稳定性下降,红细胞溶解释放的二磷酸腺苷引起血小板活化,参与动脉粥样硬化的发展。因此,Ox—LDL 对红细胞的损伤使红细胞变形性降低是动脉粥样硬化继发性改变,并且参与动脉粥样硬化的发展。
[Abstract]:The research of hemorheology is developing towards the cellular and molecular level, and the molecular biological mechanism that causes the change of the erythrocyte mechanical properties and the whole hemorheological characteristics is studied more deeply at the cellular and molecular level. It is helpful to understand the physiological and clinical significance of erythrocyte deformability and provide important basis for the basic pathological and clinical study of many diseases related to erythrocyte rheology. It is generally believed in biology and medicine that low density lipoprotein (LDL) can damage arterial endothelial cells after oxidative modification to oxidize LDL. The injured arterial endothelial cells will be transformed into foam cells, and then form as lesions, which indicates that LDL promotes the development and development of as. However, biology and medicine know little about the damage of Ox-LDL to erythrocyte. Through a large number of experimental studies, it has been proved that the main mechanical properties of erythrocyte are viscoelasticity of erythrocyte membrane. The change of viscoelasticity of erythrocyte membrane is common in organism. There is a clear correlation between the oxidative damage of membrane protein and the mechanism of oxygen free radical reaction. Therefore, the oxidative damage of erythrocyte membrane is the molecular biological mechanism that causes the change of the mechanical properties of erythrocyte membrane. (may come from different pathological or physiological reasons, but all produce oxygen free radical damage) In this study, we searched the relevant literature and applied the basic principles and experimental methods of cell rheology. The hemispherical hat model of erythrocyte membrane (constitutive relation) proposed by Chien was studied to study the effect of oxidative damage of membrane protein on the dynamic process of membrane deformation. Combined with the theory of molecular biology and biochemical analysis methods, using molecular biology technology, SDS-PAGE electrophoresis. The results showed that a new band with molecular weight higher than Spectrin appeared in the membrane proteins with oxidative damage, which would limit the spatial conformation change and resonance degree of freedom of the membrane proteins. The effects of oxidative damage of erythrocyte membrane protein on the membrane viscoelasticity and the composition of membrane protein were systematically studied. Through the research in this paper, we can conclude that the damage to red blood cells caused by w / Ox-LDL is mainly the damage of erythrocyte membrane, that is, the change of membrane protein composition, after the damage of erythrocyte membrane. The deformability of erythrocytes and the ability of oxygen delivery and oxygen release were decreased, and the deformability of erythrocytes increased blood viscosity and blood flow velocity, resulting in endothelial cell damage. Decreased erythrocyte deformability means a decrease in stability. Adenosine diphosphate, which is released from erythrocytic dissolution, causes platelet activation and is involved in the development of atherosclerosis. The decrease of erythrocyte deformability caused by Ox-LDL injury is a secondary change of atherosclerosis and is involved in the development of atherosclerosis.
【学位授予单位】：重庆大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R329.2

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