高脂血症循环白细胞自发活化作用的研究

高血脂是心脑血管病的重要危险因素。活化白细胞在缺血过程中微血管嵌塞和组织损伤中起重要作用。为了研究血清胆固醇对循环白细胞活化作用的影响，采用硝基蓝四唑试验测量了高脂血症家兔循环白细胞自发活化率（ＳＡＲ）。结果指出，高脂血症动物循环白细胞ＳＡＲ（％）显著高于对照组（Ｐ〈０．０１）。ＳＡＲ升高与血清胆固醇水平有关。循环白细胞ＳＡＲ升高导致白细胞粘附分子ＣＤ１１／ＣＤ１８表达增加和循环障碍。因此循环白细     

高血脂对血细胞和血管内皮细胞的损伤

目的研究血清胆固醇 (cho)升高和氧化低密度脂蛋白 (OX -LDL)在血细胞和血管内皮细胞 (VEC)损伤中的作用。方法采用高胆固醇血症家兔模型研究血清cho对红细胞变形性 ,白细胞自发活化率及粘附分子 (CD11b/CD18)表达的影响。采用人脐静脉内皮细胞 (HUVEC)研究OX -LDL对VEC粘附分子 (ICAM -1、VCAM -1)和MCP-1表达的影响。结果动物模型的结果指出随着血清cho升高 ,红细胞变形性降低 ,白细胞SAR和CD11b/CD18表达增加。由HUVEC获得如下结果 :(1)培养的HUVEC能少量表达ICAM -1和MCP -1及蛋白 ;(2)OX -LDL可显著增强ICAM -1、MCP -1及蛋白表达。对VCAM -1表达无影响 ;(3)OX -LDL有细胞毒性 ,引起VEC形态异常。结论血清cho升高引起红细胞变形性降低 ,白细胞SAR升高 ,活化的白细胞通过释放超氧阴离子自由基 (O·2-)和蛋白酶 ,损伤VEC ,从而破坏内皮的完整性。因此 ,血清cho升高是AS和心、脑血管病的重要危险因素之一。     

高脂血症对微循环影响机理的研究

目的高脂血症（特别是高胆固醇血症）是心脑血管病的重要危险因素,微循环是血液循环的重要功能单位,在心脑血管病中常伴有微循环的异常。本研究试图研究血清胆固醇（ＴＣ）水平与微循环改变之间的关系及其机理。方法通过实验性高胆固醇血症家兔模型研究了血清ＴＣ对全血粘度（ηｂ）、血浆粘度（ηＰ）、红细胞变形性指数（ＤＩ）及聚集状态、对循环白细胞自发活化率（ＳＡＲ）、粘附性及粘附分子ＣＤ１１／ＣＤ１８表达率的变化以及对微循环灌注状态的影响。结果表明动物以高脂食物喂养至１２周过程中血清ＴＣ水平逐渐升高,由１．３３±０．６４ｍｍｏｌ升至３８．９６±１３．２３ｍｍｏｌ．其血液粘度在自然压积下变化不显著。血浆ηｐ显著升高,由 １０７± ０． ０７ｍＰａ·ｓ升至１．３１±０．３４ｍＰａ·ｓ。红细胞ＤＩ显著降低,由３．１６±０．２４降至２．．３０±０．３４。循环白细胞ＳＡＲ显著增加,由６．９３±４．１３升至１３．４０±５．５１。白细胞的粘附性增加一倍以上。介寻白细胞粘附的粘附分了ＣＤ１３／ＣＤ１８的表达增加三倍以上,由１７．１８＿±５．４１升至５５．１０±１７．４２球结腊微循环观测显示随血清ＴＣ升高,微皿管血流变慢,红细胞聚集现象逐渐加重,     

017 高脂血症血液流变性变化机理的研究

目的: 高脂血症(特别是高胆固醇血症)是心脑血管疾病的重要危险因素, 它们的共同特点是血液流动性异常, 全身或局部血液循环和微循环障碍, 导致组织器官缺血缺氧, 进而引起新陈代谢和生理功能障碍. 以往的研究多侧重于观测一些常规血液流变学指标及微循环改变, 而细胞及分子水平上的研究较少, 故以兔高脂血症模型为对象, 将血清胆固醇(TCh)对血液流变性、红细胞变形、白细胞粘附性的影响与红细胞膜脂组成、白细胞活化状态及其粘附分子表达结合起来进行研究, 分析高脂血症血液流变性变化机理. 方法: (1) 高脂食物喂养法复制兔高脂血症模型; (2) 激光衍射法测定红细胞(RBC)的变形性; (3) 荧光偏振法测量RBC膜的流动性, 以荧光偏振度(DFP)表示; (4) NTB(硝基蓝四唑)试验检测白细胞(WBC)自发活化率(SAR); (5) 间接免疫荧光法检测WBC表面粘附分子CD11b/CD18的表达率; (6) 剪切力耐受法测WBC的粘附率. 结果: 高脂饲养四周后, TCh即由1.33±0.64 mmol/L达到21.75±14.49 mmol/L, 12周后升高至38.96±13.23 mmol/L, 血浆粘度增加20.6%, 全血粘度在同样的RBC压积下也增高了40.7%. RBC膜的胆固醇/磷脂(Ch/PL)升高23.1%, 而膜的DFP由0.267±0.026增加至0.357±0.059, 也即膜的流动性下降33.7%. 同时RBC的变形性也下降了27.2%, WBC的SAR(%)由6.93±4.13升高至13.40±5.51, 其表面粘附分子表达率增加了二倍, 粘附性也有显著增强. 结论: 结果表明, 高脂血症情况下全血粘度及血浆粘度均有升高. 由于血细胞和血清之间的脂肪分子处于动态平衡, 因此TCh升高, 必然引起RBC膜的Ch/PL升高, 导致RBC膜流动性下降. 高TCh还可激活血清补体系统产生C5b-9复合物, 进而激活WBC, 使其SAR升高、变形性下降、细胞表面粘附分子表达增加, 与补体活化产物共同促进WBC对血管内皮的粘附, 从而增加血流阻力. 活化的WBC可释放大量的超氧阴离子自由基(O-2), 引起RBC膜脂质过氧化损伤, 使RBC变形性下降、聚集性增强; O-2还可灭活内皮衍生性舒张因子(NO)的作用, 抑制血管扩张, 损伤血管内皮, 破坏内皮的完整性. 因而, 由于血脂异常引起的WBC活化并释放自由基在高脂血症的细胞及血液流变行为中起着关键作用, 在高脂血症的预防和治疗中应予以重视.     

高脂血症血液流变性变化机理的研究

目的 :高脂血症 (特别是高胆固醇血症 )是心脑血管疾病的重要危险因素 ,它们的共同特点是血液流动性异常 ,全身或局部血液循环和微循环障碍 ,导致组织器官缺血缺氧 ,进而引起新陈代谢和生理功能障碍。以往的研究多侧重于观测一些常规血液流变学指标及微循环改变 ,而细胞及分子水平上的研究较少 ,故以兔高脂血症模型为对象 ,将血清胆固醇 (ＴＣｈ)对血液流变性、红细胞变形、白细胞粘附性的影响与红细胞膜脂组成、白细胞活化状态及其粘附分子表达结合起来进行研究 ,分析高脂血症血液流变性变化机理。方法 :(1)高脂食物喂养法复制兔高脂血症模…     

急性脑梗死患者治疗前后血清Hcy和NPY检测的临床意义

文献证实，同型半胱氨酸（Hey）为心脑血管病的最危险因素。神经肽Y（NPY）可能是作为一种神经递质或调质对心血管活力发挥其调解作用。我们对急性脑梗死患者治疗前后血清Hey和NPY水平进行测定，现将结果报道如下。     

山东地区人群脂肪肝体检分析

目的 探讨山东地区体检人群中脂肪肝的发病率及脂肪肝与高脂血症的关系。方法空腹采集静脉血，测定血液总胆固醇（TC）、甘油三酯（TG）水平；通过腹部超声影像学技术进行肝脏超声检查，检测脂肪肝。结果892例体检者中脂肪肝165例，发病率为18．5％。高脂血症患者（包括高甘油三酯血症、高胆固醇血症及混合型高脂血症）216例，占被检人群的24．2％。高脂血症人群脂肪肝发病率明显高于血脂正常者（40．7％比5．18％，P〈0．01）。结论高脂血症是山东地区脂肪肝发病的显著危险因素，降脂治疗是该地区防治脂肪肝的重点。     

血脂康胶囊治疗冠心病血脂异常患者临床疗效分析

血脂异常已成为当代人类社会的普遍健康问题.大量研究证明,血清总胆固醇(TC)、甘油三酯(TG)升高,特别是低密度脂蛋白胆固醇(LDL-C)的升高,是诱发动脉硬化和冠心病的重要因素,对高脂血症进行治疗在冠心病预防中起着重要作用.本研究通过血脂康治疗冠心病血脂异常患者,以探讨其对血脂代谢的影响.     

某些血管病循环白细胞自发活化作用的研究

某些血管病循环白细胞自发活化作用的研究１金永娟２朱文云２邢海燕２吴秉权２李尚珠２由由于白细胞的抗微生物和免疫功能，传统认为白细胞对机体是有益的。但近年来的一些研究表明白细胞在一些疾病（特别是心、脑血管疾病）的早期和发展过程中起着重要作用。流行病学的研...     

糖尿病患者微循环改变与胆石症

目的 探讨Ⅱ型糖尿病微循环障碍与胆石症的关系。方法 采用病例对照研究，观察４８例Ⅱ型糖尿病合并胆石症的４８例Ⅱ型糖尿病不合并胆石症患者的微循环分值，血清甘油三酯（ＴＧ），总胆固醇（ＴＣ），高密度脂蛋白－胆固醇（ＨＤＬ－Ｃ）。结果 糖尿病合并胆石症组与不合并胆石症组相比，微循环分值较高，ＴＧ，ＴＣ明显增高，而ＨＤＬ－Ｃ无显著变化。结论 微循环障碍，高脂血症是糖尿病患者中胆石症形成的危险因素。     

皮瓣缺血再灌注损伤过程髓过氧化酶及白细胞膜CD_18的变化

目的观察大鼠岛状皮瓣在缺血再灌注损伤过程中髓过氧化酶 (MPO)含量及外周血白细胞膜CD18 的变化。方法应用大鼠腹部岛状皮瓣缺血再灌注损伤模型 ,检测皮瓣髓过氧化酶 (MPO)含量 ,测定外周血白细胞膜CD18 水平的变化并作白细胞计数。结果缺血8h及缺血再灌注1h白细胞膜CD18 水平与皮瓣MPO水平较对照组明显增高 (P<0.01) ,而缺血再灌注1h较缺血8h组又明显增高 (P<0.01)。缺血再灌注1h组外周血白细胞计数较对照组明显减少 (P<0.01)。结论大鼠岛状皮瓣缺血再灌注损伤过程中外周血白细胞膜CD18 水平增高 ,白细胞计数减少 ,皮瓣MPO水平增高。CD18 介导的白细胞粘附在皮瓣缺血再灌注损伤中起重要作用     

Propranolol affects stress-induced leukocytosis and cellular adhesion molecule expression

In this study, the impact of the beta-adrenergic antagonist propranolol on resting and acute psychological- and physical-stress-induced circulating leukocyte numbers and the density of cellular adhesion molecules was investigated. In a randomized double-blind crossover design, 45 healthy volunteers performed a 15-min public speaking task and 21 subjects performed a 16-min bicycle exercise after 5 days of ingesting a placebo and after 5 days of ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover, propranolol preferentially blunted-psychological stress-induced increases in na?ve T-helper (CD4+CD62L+; P<0.049) and na?ve T-cytotoxic lymphocytes (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+; P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced following propranolol treatment (P<0.04). In contrast to the effect on the numbers of adhesion-molecule-bearing cells, there was only a modest effect of propranolol on stress-induced alterations of the density of CD62L, CD54 and CD11a. In this study, propranolol treatment interfered with the adrenergic regulation of circulating leukocyte numbers by blunting psychological stress effects but enhancing exercise effects. Propranolol affected the cell activation status to a lesser extent, as reflected by the density of adhesion molecules.     

高脂血症血液流变与细胞流变性变化机理的研究

目的 :探讨血清胆固醇 (TCh)对血液流变性及细胞流变性的影响及其机理。方法 :分别采用激光衍射法、荧光偏振法、硝基蓝四唑(NBT)实验、间接免疫荧光法及剪切力耐受法测定红细胞 (RBC)的变形性、RBC膜的流动性、白细胞 (WBC)的活化及粘附性。结果 :随着TCh的升高 ,RBC的膜流动性降低 ,变形性下降 ,WBC的自发活化率显著升高 (P <0 .0 1) ,粘附分子表达及粘附率亦升高。结论 :由于血脂异常引起的WBC活化并释放自由基及RBC的变形性改变在高脂血症的细胞及血液液变行为中起着关键作用。     

Altered expression of L-selectin (CD62L) on polymorphonuclear neutrophils of children vertically infected with human immunodeficiency virus type 1

The expression of the leukocyte adhesion molecule L-selectin (CD62L) on polymorphonuclear neutrophils (PMN) and circulating levels of the soluble form of the receptor (sCD62L) were determined for a group of HIV-1-infected children, categorized as having mild or severe disease, and a group of uninfected control children. The fluorescence intensity of CD62L on PMN was significantly reduced in the HIV-1-infected children with mild disease compared to the uninfected controls. The proportion of lymphocytes expressing CD62L, as well as their corresponding fluorescence intensities, was significantly reduced in both the mild and the severe disease groups compared to the uninfected children, while peripheral levels of sCD62L were significantly elevated in the HIV-1-infected children with mild and severe disease compared to the controls. Altered cell migration resulting from reduced expression of CD62L may be an important contributor to the increased susceptibility to secondary microbial infections seen in HIV-1-infected children.     

Activation and interaction of CD44 and hyaluronan in immunological systems.

Adhesive interactions between receptors on vascular endothelial cells (EC) and circulating leukocytes are pivotal in regulating leukocyte extravasation. Although primary adhesion of lymphocytes to EC has been primarily attributed to the selectin family of receptors, CD44 can also mediate this function when activated to bind its ligand hyaluronan (HA). Triggering through the T cell receptor induces activated CD44 and CD44-dependent primary adhesion in both human and mouse lymphocytes, and the interaction can mediate the extravasation of activated T cells into an inflamed site. Lymphocytes capable of CD44/HA-dependent primary adhesion are found in peripheral blood of some rheumatologic patients, and their presence is associated with concurrent symptomatic or active disease. Thus, circulating T cells bearing activated CD44 may represent a pathogenically important subpopulation of activated cells that is elevated under conditions of chronic inflammation. Together, these data add to the selectin and immunoglobulin gene families a new receptor/ ligand pair and further our understanding of their potential physiological role; i.e., antigen-specific T cell activation together with local vascular inflammation permits the CD44/HA interaction and subsequent T cell extravasation.     

Peripheral blood fibrocytes from burn patients: identification and quantification of fibrocytes in adherent cells cultured from peripheral blood mononuclear cells

Peripheral blood fibrocytes are a newly identified leukocyte subpopulation that displays fibroblast-like properties. These blood-borne cells can rapidly enter the site of injury at the same time as circulating inflammatory cells. We hypothesize that circulating fibrocytes represent an important source of fibroblasts for healing of extensive burn wounds where it may be difficult for fibroblasts to migrate from the edges of uninjured tissue. In this study we identified and quantified fibrocytes among the adherent cells cultured from human peripheral blood mononuclear cells (PBMC) obtained from 18 burn patients and 12 normal individuals, based on their ability to express type I collagen. Our results showed that adherent cells cultured from PBMC of burn patients differentiated to fibrocytes more efficiently than did those from normal individuals. The percentage of type I collagen-positive fibrocytes was significantly higher for patients than for controls (89.7 +/- 7.9% versus 69.9 +/- 14.7%, p < 0.001). This percentage was consistently higher for patients with a >/=30% total body surface area burn until 1 year, with the highest percentage appearing within 3 weeks of injury. A positive correlation was found between the levels of serum transforming growth factor-beta1 (TGF-beta1) and the percentage of fibrocytes developing in the cultures of PBMC derived from these patients. We also demonstrated that fibrocytes were derived from CD14(+) cells but not CD14(-) cells. Conditioned medium from CD14(-) cells was, however, required for fibrocyte differentiation, whereas direct contact between CD14(-) and CD14(+) cells was not necessary. Treatment of the cell cultures with TGF-beta1 enhanced the development of collagen-positive cells, whereas the inclusion of neutralizing anti-TGF-beta1 antibodies in the CD14(-) conditioned medium suppressed fibrocyte differentiation. These data suggest that the development of fibrocytes is up-regulated systemically in burn patients. Increased TGF-beta in serum stimulates the differentiation of the CD14(+) cell population in PBMC into collagen-producing cells that may be important in wound healing and scarring.     

Increased circulating interleukin 10-secreting B cells in patients with dilated cardiomyopathy

Objectives: Regulatory B cells (Bregs) have recently been implicated in the pathogenesis of autoimmune diseases. However, their role in the pathogenesis of dilated cardiomyopathy (DCM) remains uncertain. We examined the levels of circulating interleukin 10 (IL-10)-secreting Bregs in patients with DCM. Methods: The frequency of CD19+IL-10+-, CD19+CD5+-, CD19+CD5+CD1d+-, and CD19+CD5+CD1d+IL-10+-B cells in peripheral blood from DCM patients, heart failure (HF) control patients, and healthy controls (HCs) were analyzed by flow cytometry. Results: DCM and HF control patients showed significantly elevated heart rate, increased left ventricular end-diastolic and left ventricular end-systolic diameters, higher levels of serum brain natriuretic peptide and reduced left ventricular ejection fraction, compared to subjects in the HC group. DCM patients showed significantly elevated levels of circulating CD19+IL-10+-, CD19+CD5+-, CD19+CD5+CD1d+-, and CD19+CD5+CD1d+IL-10+-B cells than HF control and HC patients (all P < 0.05). Conclusions: DCM patients exhibited elevated peripheral blood IL-10-secreting B cell levels, suggesting that IL-10-secreting B cells may play an important role in the pathogenesis of DCM.     

Peripheral HLA-G/ILT-2 immune checkpoint axis in acute and convalescent COVID-19 patients

The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) can elicits pro-viral activities by down-modulating immune responses. We analysed soluble forms of HLA-G, IL-6 and IL-10 as well as on immune effector cell expression of HLA-G and its cognate ILT-2 receptor in peripheral blood obtained from hospitalised and convalescent COVID-19 patients. Compared with convalescents (N = 202), circulating soluble HLA-G levels (total and vesicular-bound molecules) were significantly increased in hospitalised patients (N = 93) irrespective of the disease severity. During COVID-19, IL-6 and IL-10 levels were also elevated. Regarding the immune checkpoint expression of HLA-G/ILT-2 on peripheral immune effector cells, the frequencies of membrane-bound HLA-G on CD3+ and CD14+ cells were almost identical in patients during and post COVID-19, while the frequency of ILT-2 receptor on CD3+ and CD14+ cells was increased during acute infection. A multi-parametric correlation analysis of soluble HLA-G forms with IL-6, IL-10, activation markers CD25 and CD154, HLA-G, and ILT-2 expression on immune cells revealed a strong positive correlation of soluble HLA-G forms with membrane-bound HLA-G molecules on CD3+/CD14+ cells only in convalescents. During COVID-19, only vesicular-bound HLA-G were positively correlated with the activation marker CD25 on T cells. Thus, our data suggest that the elevated levels of soluble HLA-G in COVID-19 are due to increased expression in organ tissues other than circulating immune effector cells. The concomitant increased expression of soluble HLA-G and ILT-2 receptor frequencies supports the concept that the immune checkpoint HLA-G/ILT-2 plays a role in the immune-pathogenesis of COVID-19.     

Alteration of Some Inflammatory Biomarkers by Dietary Oxysterols in Rats

Oxysterols are structurally similar to cholesterol, but are characterized by one or more additional oxygen-containing functional groups. These compounds are implicated in inflammation given their ability to cause irreversible damage to vascular cells. The aim of this study was to study the alteration of some inflammatory biomarkers in Wistar rats in response to dietary oxysterols. Eighteen rats were randomly divided into three groups of six rats each. A standard diet supplemented with 1% (w/w) pure cholesterol (Chol group) or 1% (w/w) of an oxidized cholesterol mixture (COPs group) was fed for 8 weeks. Blood serum was separated; abdominal, pericardial, and epididymal adipose tissue was removed carefully. The COPs subjects exhibited significant increase in blood pressure and serum triacylgycerols as well as increased body fat index and pericardic, abdominal, and epididymal adipose tissue. These effects were accompanied by elevated circulating levels of plasma high-sensitivity C-reactive protein, tumor necrosis factor alpha, and resistin. We suggest that dietary oxysterols have an important pro-inflammatory effect.