低密度脂蛋白体外氧化修饰过程中几种产物变化的动力学研究

用Ｃｕ＾２＋引发低密度脂蛋白的氧化修饰，研究了低密度脂蛋白氧化修饰过程中脂氢过氧化物，共轭二烯烃，硫代巴比妥酸反应物质琼脂糖凝胶电泳迁移率和荧光物质含量变化的动力学。     

血凝集素样氧化型低密度脂蛋白受体-1在氧化型低密度脂蛋白诱导的巨噬细胞氧化应激中的作用

目的：探讨血凝集素样氧化型低密度脂蛋白受体-1(LOX-1)在氧化型低密度脂蛋白（ox-LDL）诱导的巨噬细胞氧化应激中的作用。方法：将生长至对数增殖期的巨噬细胞随机分成对照组、空质粒对照组（pCon组）、ox-LDL组、LOX-1-小干扰RNA(siRNA)+ox-LDL组,分别测定各组丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性,荧光显微镜及流式细胞仪检测各组巨噬细胞活性氧（ROS）水平,实时定量聚合酶链反应（PCR）及Western blot法检测各组还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）核心酶NOX2及亚组分p22phox的mRNA及蛋白表达水平。结果：（1）与对照组、pCon组比较,oxLDL组MDA含量明显升高,SOD活性明显下降;与ox-LDL组比较,LOX-1-siRNA+oxLDL组MDA含量明显下降,SOD活性明显升高。（2）荧光显微镜、流式细胞仪检测示oxLDL组巨噬细胞ROS平均荧光强度较正常对照组、pCon组显著增加,而LOX-1-siRNA+ox-LDL组较ox-LDL组显著降低,pCon组与对照组相比差异无统计学意义。（3）实时定量PCR及W...     

丙丁酚抑制低密度脂蛋白氧化的作用

丙丁酚是临床应用的降脂药物,由于其结构中两个羟基取代的苯环而具有断链抗氧化剂活性,可干预抵密度脂蛋白的氧化修饰,抑制氧化型低密度脂蛋白形成,从而对动脉粥样硬化的防治有重要意义。     

中药提取物对低密度脂蛋白氧化的体外抑制作用

近年发现天然多酚类化合物的抗低密度脂蛋白(LDL)氧化作用，我们研究有类似结构中药提取物的这一作用，为进一步药物研究奠定基础。     

氧化低密度脂蛋白的动脉粥样硬化

大量资料表明 ,血浆低密度脂蛋白 ( LDL )浓度升高是动脉粥样硬化 ( AS)的主要危险因素之一 ,但其机制尚未阐明。在某一特定的 LDL血浆浓度人群中 ,冠心病的发病和临床表现有很大差异。说明高脂血症与 AS的发生及冠心病的发病率和病死率之间存在复杂的多因素相互作用的机制。Steinbery等将氧化 LDL 与单核巨噬细胞( MM)的相互作用认为是粥样斑块 (脂纹 )中泡沫细胞形成的重要机制 ;而且 L DL的氧化修饰也可发生于人体 ,具有多种致 AS的细胞生物学效应 ,从而提出了动脉粥样硬化氧化修饰学说 ,具体如下。1　L DL氧化修饰过程及其理…     

轻度氧化低密度脂蛋白对巨噬细胞内质网应激的诱导作用及其信号通路

目的研究巨噬细胞泡沫化过程中轻度氧化低密度脂蛋白(mm-LDL)对巨噬细胞内质网应激的诱导作用及其信号通路。方法体外培养鼠源RAW264.7巨噬细胞,分别给予mm-LDL(25、50和100 mg/L)和衣霉素(TM)处理6、12和24 h。采用油红O染色观察细胞内脂质蓄积情况,酶比色法测定细胞内总胆固醇含量,免疫荧光细胞化学法观测转录激活因子6(ATF6)核转位情况,免疫印迹法检测内质网应激转导子1(IRE1)磷酸化水平和X盒结合蛋白1(XBP1)及内质网分子伴侣糖调节蛋白78(GRP78)蛋白的表达,RT-PCR检测GRP78 mRNA的表达。结果 mm-LDL呈浓度依赖性增加细胞内总胆固醇含量,胞浆内可见大量油红O染色阳性脂质颗粒,以12 h时最为显著;与内质网应激诱导剂TM相似,mm-LDL显著诱导ATF-6由胞浆向细胞核内转移,并上调磷酸化IRE1及其下游信号分子XBP1和GRP78蛋白的表达,且表达强度随着mm-LDL诱导浓度的增加而增强;50 mg/L mm-LDL处理组GRP78 mRNA的表达于作用后6 h即发生显著上调,为对照组的3.7倍,而蛋白表达水平也明显增加,并于12 h达到高峰,此...     

氧化型低密度脂蛋白在人外周血单核巨噬细胞中的代谢

为探讨氧化型低密度脂蛋白在人外周血单核巨噬细胞中的代谢及其致动脉粥样硬化的机制，使用放射配基法观察了两种低密度脂蛋白在单核巨噬细胞中的代谢情况，并测定了细胞内胆固醇含量的变化。结果发现，人外周血单核巨噬细胞通过受体途径代谢低密度脂蛋白。该受体可饱和，最大结合量（Bmax）为274μg／g细胞蛋白，解离常数为35.7mg／L。低密度脂蛋白经氧化修饰后，人外周血单核巨噬细胞对其结合、摄取和降解均显著增加；与氧化型低密度脂蛋白共同孵育的人外周血单核巨噬细胞内总胆固醇含量明显高于低密度脂蛋白组。以上结果提示，低密度脂蛋白经氧化修饰后在人外周血单核巨噬细胞内的代谢途径发生改变并导致细胞内总胆固醇的堆积，促进了动脉粥样硬化的发生。     

微量元素在低密度脂蛋白氧化修饰过程中的作用

微量元素在低密度脂蛋白氧化修饰过程中的作用山东医科大学附属医院心内科田庆印庆云县医院内科王兴东综述潘其兴审校近年证实，氧化修饰低密度脂蛋白（ｏｘｉ－ｄｉｚｅｄｌｏｗｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎ，ＯＸ－ＬＤＬ）在动脉粥样硬化（ＡＳ）发生发展过程...     

氧化的低密度脂蛋白与动脉粥样硬化

氧化ＬＤＬ存在并为粥样硬化斑块始发的中心环节，抗氧化剂能抑制体内的脂蛋白氧化，并对粥样硬化的发生有保护作用。相当多的证据表明抗氧化的维生素可降低冠心病的危险性。     

氧化型低密度脂蛋白的不同组分在诱导巨噬细胞凋亡中的作用

通过观察调居噬细胞的特征性ＤＮＡ梯形图谱和细胞核的形态变化，研究了氧化型低密度脂蛋白的不同组份在其诱导的巨噬细胞凋亡中的作用。结果发现；氧化型低密度脂蛋白可引起巨噬细胞凋亡，表现在ＤＮＡ图谱呈典型的梯形，细胞核固缩，正常和乙酰化低密度脂蛋白均未引起巨噬细胞的明显凋亡，用谷胱苷肽过氧化物酶模拟物ｅｂｓｅｌｅｎdisplay structure     

ATP7B基因突变致肝豆状核变性的分子机制研究进展

肝豆状核变性,即Wilson病,是一种由铜离子转运ATP酶β肽(ATPase Cu2+transporting beta polypeptide,ATP7B)基因突变导致的常染色体隐性遗传的铜代谢障碍性疾病。现归纳总结不同突变的致病机制,包括诱导突变蛋白错误定位、改变蛋白间或结构域间相互作用、调控ATP7B蛋白催化活性、改变ATP7B基因剪接方式等多个方面。临床上,系统总结了常见突变与临床表型间的关联,如p.R778L,被认为与更加严重的临床症状相关;同时,环境、饮食、生活习惯等因素的差异亦可能对患者是否发病或发病时间产生较大影响。在分子层面上对ATP7B基因突变致病机制及所致临床表征的研究进行综述,将有助于加深对肝豆状核变性发病机制的认识,并提示可针对不同的机制采用个性化的诊疗手段,以指导临床实践。     

Microstructure and Mechanical Properties of Composites Obtained by Spark Plasma Sintering of Ti3SiC2-15 vol.%Cu Mixtures

Method of soft metal (Cu) strengthening of Ti₃SiC₂ was conducted to increase the hardness and improve the wear resistance of Ti₃SiC₂. Ti₃SiC₂/Cu composites containing 15 vol.% Cu were fabricated by Spark Plasma Sintering (SPS) in a vacuum. The effect of the sintering temperature on the phase composition, microstructure and mechanical properties of the composites was investigated in detail. The as-synthesized composites were thoroughly characterized by scanning electron micrography (SEM), optical micrography (OM) and X-ray diffractometry (XRD), respectively. The results indicated that the constituent of the Ti₃SiC₂/Cu composites sintered at different temperatures included Ti₃SiC₂, Cu₃Si and TiC. The formation of Cu₃Si and TiC originated from the reaction between Ti₃SiC₂ and Cu, which was induced by the presence of Cu and the de-intercalation of Si atoms Ti₃SiC₂. OM analysis showed that with the increase in the sintering temperature, the reaction between Ti₃SiC₂ and Cu was severe, leading to the Ti₃SiC₂ getting smaller and smaller. SEM measurements illustrated that the uniformity of the microstructure distribution of the composites was restricted by the agglomeration of Cu, controlling the mechanical behaviors of the composites. At 1000 °C, the distribution of Cu in the composites was relatively even; thus, the composites exhibited the highest density, relatively high hardness and compressive strength. The relationships of the temperature, the current and the axial dimension with the time during the sintering process were further discussed. Additionally, a schematic illustration was proposed to explain the related sintering characteristic of the composites sintered by SPS. The as-synthesized Ti₃SiC₂/Cu composites were expected to improve the wear resistance of polycrystalline Ti₃SiC₂.     

尿毒症患者红细胞膜泵功能的研究

本文对32例尿毒症及透析治疗患者的红细胞膜Ca~(2+)-Mg~(2+)+ATP酶和Na~+-K~+ATP酶活性及红细胞内钙、钠离子浓度进行同步测定。发现尿毒症患者的Ca~(2+)-Mg~(2+)ATP酶和Na~+-K~+ATP酶活性降低,红细胞内钙、钠浓度升高,经透析治疗2～3个月后,尿毒症患者血清中分子水平降低,Ca~(2+)-Mg~2+AI"P瞎和Na+.K+ATP酶活性恢复.此外,我们还测定了一次血透前后血浆钙及全血离子钙浓度的变化;并将尿毒症组与同期透析治疗组各项指标作了比较,结果发现同期透析治疗患者的膜泵功能明显恢复,血清钙浓度得到纠正.     

Pathogenetic analysis of three cases with a bleeding disorder characterized by defective platelet aggregation induced by Ca2+ ionophores

We report three cases of platelet dysfunction characterized by defective Ca2+ ionophore-induced platelet aggregation without impaired production of thromboxane A2 (TXA2). The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable TXA2 (STA2) and Ca2+ ionophore A23187 was defective or much reduced. However, ristocetin- or thrombin-induced platelet aggregation was normal. The analysis of second messenger formation showed that inositol 1,4,5-triphosphate formation or Ca2+ mobilization induced by thrombin, STA2 or A23187 was normal. Furthermore, the phosphorylation of 47 kDa protein (pleckstrin) and 20 kDa protein (myosin light chain, MLC) in response to those agonists was normal. These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca2+ mobilization and MLC phosphorylation.     

Selected Properties of a Zr-Containing AlSi5Cu2Mg Alloy Intended for Cylinder Head Castings

The aim of this paper was to analyze the impact of the addition of different amounts of zirconium (0.05; 0.10; 0.15 and 0.20 wt. % Zr in the form of the AlZr20 master alloy) on selected properties of AlSi5Cu2Mg aluminum alloy. This is a new alloy for cylinder head castings and has only been used for a relatively short time. The specificity of this alloy is its chemical composition—specifically the low permitted Ti content, which makes it impossible to refine the grain structure of this alloy using standard Al-Ti-B grain refiners. The aim of our ongoing research is to find a suitable alloying element that would positively mainly affect the mechanical and also physical properties of this alloy, which are crucial for complex automotive castings such as cylinder heads. The results of our research showed that increasing zirconium content had no effect on the increase in ultimate tensile strength, yield strength and hardness of as-cast samples. After T7 heat treatment, a more significant increase in UTS, YS and thermal conductivity occurred due to the precipitation of Cu- and Mg-rich strengthening precipitates. Zirconium-rich intermetallic phases were observed in the shape of separate thick needles or as a cluster of two crossed thinner needles. SEM observations showed that these phases crystallized near to the intermetallic phases based on Cu and Fe. Increasing the Zr content was accompanied by an increase in liquidus temperature, the density index and the area fraction of porosity values.     

(Ca2++Mg2+)-ATPase activity of sickle cell membranes: decreased activation by red blood cell cytoplasmic activator.

Human red blood cells (RBCs) contain a cytoplasmic protein that activates membrane-bound (Ca2+ + Mg2+)-ATPase and the transport of Ca2+. The (Ca2+ + Mg2+)-ATPase of sickle cells showed a less than normal response to this activator. This was true whether the activator was obtained from normal or sickle cells. Activator present in sickle cell hemolysates fully activated the (Ca2+ + Mg2+)-ATPase of normal RBC membranes. These results demonstrate that membranes of sickle cells are defective in their response to the activator. Neither the apparent affinity for calcium nor the apparent affinity for activator was different comparing the (Ca2+ + Mg2+)-ATPase of sickle and normal membranes. Young, mature, and irreversibly sickled cells were separated by density gradient centrifugation, and membranes were prepared from each of these cell populations. No significant differences in ATPase activities were found based on cell age (density). The (Ca2+ + Mg2+)-ATPase of all populations of sickle cells showed a decreased response to the activator. Thus, it appears unlikely that the decreased response of the (Ca2+ + Mg2+)-ATPase of sickle cells is due to membrane damage caused by repeated sickling during the life-span of the cell. Reduced activation of (Ca2+ + Mg2+)-ATPase by the cytoplasmic activator may account for calcium accumulation in sickle cells.     

Microstructure and Mechanical Properties of Ultrafine-Grained Copper by Accumulative Roll Bonding and Subsequent Annealing

Recently, the accumulative roll bonding (ARB) technique has made significant progress in the production of various ultrafine-grained (UFG) metals and alloys. In this work, a UFG copper sheet was produced by ARB and subsequent annealing at 300 °C for 60 min to optimize strength and ductility. It was found that homogeneous lamellar UFG materials with a thickness of 200–300 nm were formed after six ARB passes. The microhardness and tensile strength of as-ARBed Cu increased, while the ductility and strain hardening decreased with the cumulative deformation strain. The as-ARBed specimens fractured in a macroscopically brittle and microscopically ductile way. After annealing, discontinuous recrystallization occurred in the neighboring interface with high strain energy, which was prior to that in the matrix. The recrystallization rate was enhanced by increasing the cumulative strain. UFG Cu ARBed for six passes after annealing manifested a completely recrystallized microstructure with grain sizes approximately ranging from 5 to 10 μm. Annealing treatment reduced the microhardness and tensile strength but improved the ductility and strain hardening of UFG Cu. As-annealed UFG-Cu fractured in a ductile mode with dominant dimples and shear zones. Our work advances the industrial-scale production of UFG Cu by exploring a simple and low-cost fabrication technique.     

Study on the Evolution of Graphene Defects and the Mechanical and Thermal Properties of GNPs/Cu during CVD Repair Process

Graphene has extremely high theoretical strength and electrothermal properties, and its application to Cu-based composites is expected to achieve a breakthrough in the performance of existing composites. As a nano-reinforced body, graphene often needs a long time of ball milling to make it uniformly dispersed, but the ball milling process inevitably brings damage to the graphene, causing the performance of the composite to deviate from expectations. Therefore, this paper uses CH₄ as a carbon source to repair graphene through a CVD process to prepare low-damage graphene/Cu composites. The process of graphene defect generation was studied through the ball milling process. The effects of defect content and temperature on the graphene repair process were studied separately. The study found that the graphene defect repair process, the decomposition process of oxygen-containing functional groups, and the deposition process of active C atoms existed simultaneously in the CVD process. When the repair temperature was low, the C atom deposition process and the oxygen-containing functional group decomposition process dominated. In addition, when the repair temperature is high, the graphene defect repair process dominated. 3 wt% graphene/Cu composites were prepared by pressure infiltration, and it was found that the bending strength was increased by 48%, the plasticity was also slightly increased, and the thermal conductivity was increased by 10–40%. This research will help reduce graphene defects, improve the intrinsic properties of graphene, and provide theoretical guidance for the regulation of C defects in composites.     

Effect of Zn and Cu Addition on Mechanical Properties of As-Extruded Mg-3Sn-1Ca Alloy

The effects of Zn and Cu addition on the microstructure and mechanical properties of the extruded Mg-3Sn-1Ca alloy were systematically studied. The effects of the grain size, texture, type and distribution of the second phase on the mechanical properties of the alloy were analyzed. The mechanical test results show that the addition of Zn and Cu elements can significantly improve the mechanical properties of the alloy. The as-extruded Mg-3Sn-1Ca-1Zn-1Cu alloy has the best comprehensive mechanical properties, and the UTS, YS and E_L are 244 MPa, 159 MPa and 13.4%, respectively. Compared with the Mg-3Sn-1Ca alloy, the UTS and E_L of the Mg-3Sn-1Ca-1Zn alloy are increased by 50 MPa and 132%, respectively. However, the UTS of the TXC311 alloy is increased by 55 MPa, but the ductility of the Mg-3Sn-1Ca-1Cu alloy is far less than that of the Mg-3Sn-1Ca-1Zn alloy, which is mainly attributed to the presence of a large amount of hard and brittle Mg2Cu phase in the alloy. Interestingly, the addition of Zn to Mg-3Sn-1Ca-1Cu alloy can improve the elongation of the alloy, which is due to the solid solution strengthening caused by the Zn element and the formation of small MgZnCu phase with Zn element and the consumption of Mg2Cu phase.