脂质对大鼠肝星状细胞低密度脂蛋白、高密度脂蛋白受体的影响

目的研究脂质（甘油三酯和极低密度脂蛋白）对大鼠HSC低密度脂蛋白（low-densitylipoprotein，LDL）、高密度脂蛋白（high-densitylipoprotein，HDL）受体的影响。方法用链霉蛋白酶和胶原酶原位灌流，Nycodenz密度梯度离心分离大鼠HSC；应用125I-LDL和125I-HDL3配体进行放射性配基结合实验测定脂质对HSC膜LDL、HDL受体的影响。结果HSC膜表面存在LDL、HDL受体;脂质可增加LDL受体对LDL的亲合力，但降低HDL受体对HDL3的亲合力。结论HSC膜上的LDL、HDL受体对脂蛋白代谢及胆固醇的调节有重要作用,为阐明脂肪肝肝纤维化的发生提供了新的实验依据。     

抗极低密度脂蛋白受体多克隆抗体的制备及鉴定

为制备抗极低密度脂蛋白受体的多克隆抗体，以极低密度脂蛋白受体配体结合域上特定片段的合成肽免疫新西兰家兔，收集免疫前后动物的血清，通过酶联免疫吸附法及免疫印迹法对血清中抗体进行分析和鉴定。结果发现，已获得高效价的抗极低密度脂蛋白受体血清，可利用免疫印迹法检测人、鼠组织和细胞中的天然极低密度脂蛋白受体及其亚型的蛋白。此结果提示，抗极低密度脂蛋白受体多克隆抗体的制备为从蛋白水平研究极低密度脂蛋白受体提供了有效的工具。     

肥胖儿童血清脂蛋白(a)水平及载脂蛋白(a)的遗传表型研究

本文对肥胖儿血清脂蛋白水平及血清载脂蛋白多态性进行分析，以探讨肥胖儿与高脂蛋白血症的关系及其血清载脂蛋白遗传表型的分布特点。用酶联免疫吸附法５７名肥胖儿及其双亲血清脂蛋白含量，用十二守基碘酸钠－聚丙烯酰胺凝胶电泳和Ｗｅｓｔｅｒｎ ｂｌｏｔ免疫印迹技术测定载脂蛋白遗传表型。     

调肝导浊中药对血载脂蛋白含量及肝细胞膜脂蛋白受体的影响

为观察调肝导浊中药对血载脂蛋白的含量及肝细胞膜脂蛋白受体的影响。采用高胆固醇饮食造成动脉粥样硬化家兔模型，用免疫比浊法测定载脂蛋白AI和载脂蛋白B含量，体外培养大鼠肝细胞，将氧化型低密度脂蛋白直接加入培养液，采用原位杂交技术观察它对肝细胞膜脂蛋白受体的影响及调肝导浊中药对其的调节作用。结果发现，调肝导浊中药可有效升高载脂蛋白AI含量和降低载脂蛋白B含量，提示调肝导浊中药对脂蛋白受体途径具有良好的调节作用，可有效调节与脂质代谢密切相关的因素。从而防治高脂血症，抑制动脉粥样硬化的形成发展。     

Alzheimer微管相关蛋白tau在猴脑中的分布及意义

目的 研究Alzheimer微管相关蛋白tau在老年猴脑中的分布，探讨老年猴是否能作为Alzheimer氏病(AD)神经原纤维缠结(NFT)病变动物。方法 应用免疫组织化学法检查老年猴脑组织广泛部位中tau蛋白沉积，并与传统的神经病理技术Glee-Marsland氏法银染色对比。应用免疫印迹法(Western blot)检查老年猴脑组织内tau蛋白与人类脑组织内tau蛋白的免疫活性蛋白电泳带的分子量范围的一致性。结果 老年猴脑海马、扣带回、颞叶及额叶脑皮质的锥体神经元的胞体、轴突及星形细胞的胞浆可见条状、块状或卷发状，缠结样免疫活性物质沉着。tsu蛋白的免疫组织化学染色方法较Glee-Marsland法银染色敏感而可靠。老年猴脑组织内tau蛋白与人类脑组织的tau蛋白免疫活性蛋白电泳带的分子量范围具有一致性。结论 老年猴脑中有类似人AD的NFT病变。老年猴可直接作为AD研究的动物模型的可能性。     

氧化型低密度脂蛋白和氧化型高密度脂蛋白对ECV304细胞Toll样受体2和Toll样受体4表达的影响及其对人单核细胞的趋化作用

目的观察氧化型低密度脂蛋白和氧化型高密度脂蛋白对ECV304细胞膜上Toll样受体2、Toll样受体4受体表达的影响,及其受这两种脂蛋白刺激后ECV304对THP-1的趋化作用。方法用不同浓度的氧化型低密度脂蛋白和氧化型高密度脂蛋白孵育ECV304细胞,用RT-PCR的方法检测细胞Toll样受体2和T     

猴脑中Alzheimer前体蛋白A4的分布及意义

目的研究老年猴脑中Alzheimer前体蛋白A4(AppA4)的分布，探讨老年猴作为Alzheimer病(AD)淀粉样蛋白沉积动物模型的可能性。方法应用免疫组织化学法检查老年猴脑组织广泛部位中AppA4的沉积，并且与传统的神经病理技术刚果红染色相对比。应用免疫印迹法(Western印迹法)检查其脑组织内AppA4与人类脑组织内AppA4的免疫活性蛋白电泳带的分子量范围的一致性。结果老年猴脑海马、扣带回、颞叶及额叶脑皮质的锥体神经元的胞体、轴丘及近端树突AppA4免疫活性物质沉着，上述部位脑皮质细胞外可见斑块样沉积，部分皮质小动脉壁可见AppA4免疫活性物质沉积。AppA4免疫组织化学染色方法较淀粉样蛋白组化方法敏感而可靠。老年猴脑组织内AppA4与人类脑组织的AppA4免疫活性蛋白电泳带的分子量范围具有一致性。结论老年猴脑中有类似人AD的淀粉样蛋白沉积病变，有作为淀粉样蛋白沉积动物模型的可能性。     

DiI标记脂蛋白改良法的建立

为了改进脂蛋白的荧光标记方法 ,本实验采用经超速离心后的离心管底层血清取代商品化的去脂血清作为脂蛋白标记时的介质 ,与荧光染料DiI混合孵育。经超速离心分离后获得DiI标记的极低密度脂蛋白、低密度脂蛋白及β 极低密度脂蛋白。本方法在标记过程中不用去脂血清 ,降低了标记成本并缩短了超速离心时间。配体与受体结合实验结果发现 ,用本方法标记的脂蛋白能以可饱和方式结合体外培养的小鼠腹腔巨噬细胞和中国仓鼠卵母细胞。表明本方法标记的脂蛋白保持了正常脂蛋白的配体功能 ,适用于脂蛋白受体的研究     

过氧化体增殖物激活型受体-γ对巨噬细胞脂蛋白受体和炎症因子表达效应的研究

目的 探讨配体曲格列酮（Trog)活化的过氧化体增殖物激活型受体γ（PPAR-γ）对脂蛋白介导的巨噬细胞脂蛋白受体和炎症因子表达的影响。方法 采用密度梯度超速离心法获得低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL），用Cu^2 LDL氧化修饰为氧化LDL；通过免疫组织化学，Northern杂交和激光扫描共聚焦显微镜检测巨噬细胞清道夫受体A（SRA），VLDL受体（VLDLR），肿瘤坏死因子-α（TNF-α）和基质金属蛋白酶-9（MMP-9）以及PPAR-γ的表达或活化状态，结果 Trog活化的PPAR-γ能抑制巨噬细胞SRA，VLDLR，TNF-α和MMP-9的mRNA以及蛋白表达。结论 PPAR-γ抑制巨噬细胞脂质摄取和炎症因子表达的效应，对防治急性冠状动脉综合征可能起着一定的作用。     

幽门螺杆菌脂蛋白Lpp20的研究进展

Lpp20是一种保守的幽门螺杆菌膜相关脂蛋白,他含有细菌脂蛋白的典型信号肽.近几年研究显示,Lpp20具有良好的免疫原性和免疫保护性.本文即对Lpp20的结构及其免疫原性和免疫保护性的研究进展作一综述.     

ENDOTHELIAL CELL SURFACE ACTIN SERVES AS A BINDING SITE FOR PLASMINOGEN, TISSUE PLASMINOGEN ACTIVATOR AND LIPOPROTEIN(a)

One of the mechanisms by which endothelial cells (ECs) regulate fibrinolysis is through the regulated assembly of proteins such as plasminogen, tissue plasminogen activator (tPA) and urokinase (uPA) on their membrane surface. Receptors for many of these fibrinolytic factors have been isolated and characterized. A unique 45 kD plasminogen receptor present on ECs derived from vein vasculature has been identified and resolved into two plasminogen binding components. One component consists of the unique 45 kD plasminogen receptor (pI = 6.3) whereas the other component (pI = 5.1) is identified as the cytoskeletal protein, actin. Immunofluorescent studies of isolated ECs confirm the presence of actin on their extracellular surface. This observation is consistent with a number of other recent reports of actin externally localized on other cell types. In vitro studies using purified actin confirm that plasminogen binds to actin both saturably and with relatively high affinity. Competition studies with lysine indicated that the binding was largely kringle-dependent, and when binding of tPA to actin was assessed, it also bound to actin with 70–80% of binding inhibited by lysine. Lipoprotein(a), which shows homology with plasminogen, also interacted with actin. Addition of plasminogen and low-density lipoproteins inhibited Lp(a) binding to actin in a dose-dependent fashion. Moreover, in competition with tPA, partial inhibition of plasminogen binding to actin was also observed. In experiments using anti-actin antibodies added in excess to cultured ECs, binding of plasminogen was inhibited by 45%, tPA binding was inhibited by 46% and Lp(a) binding was reduced by 56%, confirming actin as a binding site for these various ligands whilst attesting to the presence of other EC receptors for these proteins. Collectively, the data presented are consistent with actin playing a major role in localizing binding not only of plasminogen, but also of tissue plasminogen activator and Lp(a) to the surface of human endothelial cells.     

去唾液酸对低密度脂蛋白和脂蛋白(a)代谢的影响

将低密度脂蛋白和脂蛋白（ａ）用神经氨酸酶处理，去除低密度脂蛋白（ａ）中所含末端唾液酸，然后用＾１２５Ｉ－纤维素二糖酪胺标记，经刺猬腋下静脉注射，分别于３ｈ和６ｈ处死，测定血，肝，脾，肾和胆汁中放射含量，分析和比较去唾液酸和富含唾液酸低密度脂蛋白和脂蛋白（ａ）的代谢变化，实验发现，注射去唾液酸低密度脂蛋白的最初３ｈ，组织内的代谢速率低于低密度脂蛋白组，后６ｈ后代谢速率则高于低密度脂蛋白组。注射去唾液     

Plasmin Activation System in Restenosis: Role in Pathogenesis and Clinical Prediction?

During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis and restenosis. Responsible pathophysiologic mechanisms, however, remain elusive. This review focuses primarily on the clinicians, point of view, suggesting that increases in plasminogen activator inhibitor type-1 (PAI-1) plasma levels after balloon angioplasty or permanently elevated lipoprotein (a) (Lp(a)) plasma levels might be helpful in the prediction of restenosis after coronary angioplasty. In contrast, tissue-type plasminogen activator (tPA) plasma levels appear unrelated to restenosis, and data regarding a possible role of urokinase-type plasminogen activator (uPA) in circulation are not available at present. Furthermore, a new hypothesis on the pathophysiological role of local PAI-1 overexpression as a beneficial negative feedback mechanism to limit excess cellular proliferation in atherogenesis and restenosis is presented.     

Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a)

Objectives. Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a).
Design, setting and subjects. Healthy Norwegians 40–42 years of age, who habitually consumed five or more cups of boiled coffee per day ( n =150) were compared with matched filter coffee consumers ( n =159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992.
Results. The median lipoprotein(a) level was 13.0 mg  dL⁻¹ (10th and 90th percentile: 2.5 and 75.0 mg  dL⁻¹, respectively) on boiled and 7.9 mg dL^-1 (10th and 90th percentile: 1.9 and 62.5 mg dL⁻¹, respectively) on filter coffee ( P =0.048). Means±SE were 25.8±2.4 mg dL⁻¹ and 19.6±2.0 mg dL⁻¹, respectively ( P =0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups.
Conclusion. Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.     

The plasma membrane origin of liver-specific protein (LSP)

ABSTRACT— Liver-specific lipoprotein (LSP) is a potentially important target antigen for autoimmune liver cell injury, but the complexity of LSP “the preparation” has hindered investigation of anti-LSP immune responses. In the present study, rabbit LSP and isolated liver plasma membranes (LPM) were compared using electron microscopy and marker enzyme analysis to determine the subcellular site of origin of LSP. These results suggest that LSP “the preparation” is highly enriched with plasma membrane.     

Lipoprotein (a): Structure,Pathophysiology and Clinical Implications

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.     

Lipoprotein apheresis for the treatment of elevated circulating levels of lipoprotein(a): a critical literature review

Lipoprotein(a), which consists of a low-density lipoprotein (LDL) particle linked to an apolipoprotein(a) moiety, is currently considered an independent risk factor for cardiovascular disease due to its atherogenic (LDL-like) and prothrombotic (plasminogen-like) properties. The aim of this review is to provide an overview of the current and newer therapies for lowering increased lipoprotein(a) levels, focusing on lipoprotein apheresis. After a systematic literature search, we identified ten studies which, overall, documented that lipoprotein apheresis is effective in reducing increased lipoprotein(a) levels and cardiovascular events.     

Plasma lipoprotein(a) concentration and phenotypes in diabetes mellitus

Summary Patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are at increased risk of developing atherosclerotic vascular diseases. A variety of lipoprotein abnormalities have been described as being associated with this increased risk. In this study, apo(a) isoform frequencies and lipoprotein(a) [Lp(a)] concentrations were determined in Type 1 and Type 2 diabetic patients in order to investigate a possible contribution of Lp(a) to the increased risk for atherosclerosis in diabetes. No significant differences in plasma Lp(a) concentrations were found in two ethnically different populations (Austrians from the province of Tyrol and Hungarians from Budapest) in either type of diabetes when compared to respective control groups (91 Type 1 and 112 Type 2 diabetic patients vs 202 control subjects in the Hungarian study and 44 Type 1 diabetic and 44 Type 2 diabetic vs 125 control subjects in the Austrian study). There were also no significant apo(a) isoform frequency differences between both patient groups and control subjects in the two study groups. These data, obtained from two large ethnically different populations, provide no evidence of a contribution of Lp(a) to the increased risk for atherosclerosis in diabetes.