步行运动试验对充血性心力衰竭患者血浆可溶性炎性细胞因子和氧化应激的影响

目的：采用6min步行运动试验,观察充血性心力衰竭（CHF）患运动前后血浆肿瘤坏死因子α(TNF-α）、可溶性Fas、可溶性细胞间黏附分子－1（sICAM-1)、一氧化氮（NO）和丙二醛（MDA）等因子的变化,以及运动训练对其的影响。方法：50例CHF患和20例健康对照进行了6min步行运动试验,并于运动前及运动后抽取静脉血;血浆TNF－α、可溶性Fas和sICAM-1的含量测定采用双抗体夹心法;NO和MDA的含量测定采用比色法。10例患运动1个朋后进行了随访。结果：CHF组的基础状态血浆TNF－α、可溶性Fas、sICAM-1、MDA和NO的含量均高于对照组;6min步行运动后,对照组上述指标明显改变,而CHF患运动后即刻血浆TNF－α、可溶性Fas、sICAM-1和NO水平较运动前显增加,血浆MDA含量在运动后30min增加达高峰。运动训练1个月后的随访表明,无论基础状态还是运动后CHF患血浆TNF－α、可溶性Fas、sICAM-1、NO、MDA的水平均较前次实验明显降低。尽管第2次实验运动后即刻血浆可溶性细胞因子和氧化应激水平高于运动前,但均低于或与治疗前的基础状态差异无显性。结论：CHF患较正常人运动耐受性降低,接近CHF患日常生活活动的运动将短时间增强血浆可溶性细胞因子和氧化应激水平。     

可溶性粘附分子与冠状动脉支架植入后心脏事件的关系

目的:检测冠心病患者冠状动脉支架植入前的可溶性细胞粘附分子水平,探讨其与以后以发生心脏事件的关系。方法:对2000年4月～2002年3月在我院接受冠状动脉支架植入的107例患者,以ELISA法检测支架植入前基础血浆可溶性粘附分子水平,并进行随访。结果:20例患者失访,随访率81.3％,随访时间3～24(平均17.4)月。随访期间心绞痛症状复发13例(14.9％),非致命性心梗2例(2.3％),猝死1(1.1％)。发生心脏事件组基础可溶性细胞间粘附分子-1(sICAM-1)水平较无心脏事件组升高(P<0.01),而可溶性血管细胞粘附分子-1(sVCAM-1)、可溶性E选择素(sE-selectin)水平在两组间无显著性差异(P>0.05)。以Kaplan-Meier法计算无心脏事件生存率,slCAM-1≥276ng/ml组2年无心脏事件生存率为67.8％,而sICAM-1<276ng/ml组为88.4％,两组间有显著性差异(P<0.01)。结论:冠状动脉支架植入前基础血浆sICAM-1水平升高的患者术后无心脏事件生存率低,sICAM-1可作为冠状动脉支架植入后心脏事件发生的预测指标。     

氟伐他汀对充血性心力衰竭患者血清sICAM-1和sVCAM-1的影响

目的:探讨氟伐他汀短期治疗对充血性心力衰竭(CHF)患者血清中可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)和肿瘤坏死因子α(TNF-α)水平的影响。方法:将97例CHF患者随机分为对照组(常规治疗组)和试药组(氟伐他汀组)。采用ELISA测定治疗前及治疗两周后血清中sICAM-1、sVCAM-1和TNF-α水平。结果:两种方法都可以明显降低血清sICAM-1、sVCAM-1和TNF-α水平(P0.05);试药组血清TNF-α水平降低更为显著(P0.05),但血清sICAM-1和sVCAM-1降低水平与对照组无显著差别。结论:在常规治疗基础上短期加用氟伐他汀治疗不能进一步降低CHF患者血清sICAM-1和sVCAM-1水平。     

氟伐他汀对心力衰竭患者血清可溶性细胞黏附分子的影响

目的:观察氟伐他汀短期治疗对充血性心力衰竭(congestive heart failure,CHF)患者血清中可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)、可溶性选择素E(sE- selectin)、可溶性选择素P(sP- selectin)和可溶性选择素L(sL- selectin)水平的影响,探讨氟伐他汀对CHF的治疗作用.方法:将70例CHF患者随机分为常规治疗组和干预组(氟伐他汀组).正常对照组20例.采用酶联免疫吸附法(ELISA)测定其治疗前后血清中sICAM-1、sVCAM-1、sE- selectin、sP- selectin和sL- selectin水平.结果:血清可溶性细胞黏附分子(soluble cell adhesion molecules ,sCAM)水平在心功能Ⅳ级明显高于心功能Ⅱ、Ⅲ级患者,而心功能Ⅱ、Ⅲ级之间比较差异无统计学意义,心功能Ⅱ-Ⅳ级的患者sCAM水平均高于正常对照组(P<0.05或P<0.01).常规治疗组和干预组治疗后血清sCAM水平均较治疗前有显著下降(P<0.05或P<0.01),但干预组较常规治疗组仅sVCAM-1和sE- selectin下降水平显著(P<0.05),余各血清sCAM水平组间比较差异无统计学意义(P>0.05).结论:CHF患者血清sCAM水平下降主要与心功能改善相关,在CHF常规治疗的基础上短期加用氟伐他汀治疗能降低sVCAM-1和sE-selectin水平.     

有氧运动对急性冠脉综合征患者血清黏附分子和C反应蛋白的影响

目的: 探讨有氧运动对急性冠脉综合征(ACS)患者可溶性细胞间黏附分子-1(sICAM-1)、血管细胞黏附分子-1(sVCAM-1)和C反应蛋白(CRP)水平的影响。方法: 选取ACS患者70例,将其分为常规治疗组和有氧运动+常规治疗组（加有氧运动组）。另选健康成人为正常对照组。采用酶联免疫吸附法测定各组sICAM-1和sVCAM-1 水平,采用免疫浊度法测定CRP浓度。结果: ACS 患者循环血中sICAM-1、sVCAM-1和CRP水平明显高于正常对照组(P<0.01),两组治疗1个月后sICAM-1、sVCAM-1和CRP水平均较治疗前均明显下降(P<0.05和P<0.01)。且两组各项指标比较,加有氧运动组降低更显著(P<0.05)。结论: ACS 患者血清中sICAM-1、sVCAM-1和CRP水平明显升高,而有氧运动能明显降低ACS患者血中sICAM-1、sVCAM-1和CRP水平。     

老年ACS患者血浆sICAM-1和sE-selectin的表达及阿托伐他汀对其影响

目的探讨老年急性冠脉综合征（ACS）患者血浆可溶性细胞间黏附分子-1（sICAM-1）和可溶性E-选择素（sE-selectin）的表达及阿托伐他汀对其影响。方法用ELISA法测定90例ACS患者和40例稳定性心绞痛（SAP）患者血浆sICAM-1和sE-selectin水平。同时将ACS患者随机分为高脂血症常规治疗组（A组）、高脂血症阿托伐他汀治疗组（B组）、非高脂血症常规治疗组（C组）、非高脂血症阿托伐他汀治疗组（D组）;B、D组在常规治疗的基础上每日口服10 mg阿托伐他汀,共8周。检测各组治疗前后血浆sICAM-1和sE-selectin水平变化。结果ACS组sICAM-1和sE-selectin水平均高于SAP组（P〈0.05,〈0.01）;阿托伐他汀治疗后,B、D组sICAM-1和sE-se-lectin水平较治疗前降低。结论血浆sICAM-1和sE-selectin水平与不同类型冠心病斑块稳定性有关,阿托伐他汀具有抑制细胞黏附分子表达,稳定动脉粥样硬化斑块的作用。     

肝硬化患者血浆ET-1、NO和黏附分子的水平变化及临床意义

目的观察肝硬化患者血浆中内皮素(ET-1)、一氧化氮(NO)和可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)的水平变化及其与肝功能的关系,探讨其临床意义。方法采用放射免疫、分光光度及单克隆抗体法,分别检测肝硬化患者血浆中的ET-1、NO和sICAM-1、sVCAM-1水平并与正常对照组进行对比分析。结果肝硬化组(观察组)血浆ET-1、NO和sI-CAM-1、sVCAM均明显高于对照组。肝功能Child-Pugh分级A级与对照组之间无明显差异(P>0.05),B、C级与对照组之间差异显著(P<0.01),A、B、C级之间的差异非常显著(P<0.01)。结论肝硬化患者血浆ET-1、NO和sICAM-1、sVCAM-1水平均升高,并与肝细胞损伤、肝功能障碍呈正相关,提示血浆ET-1、NO和sICAM-1、sVCAM-1水平监测可作为临床观察肝硬化患者病变活动的重要免疫学指标,对肝硬化的早期诊断和Child-Pugh分级具有一定的参考和补充价值。     

系统性红斑狼疮患者血清可溶性黏附分子的检测

目的检测系统性红斑狼疮(SLE)患者血清黏附分子中可溶性血管细胞黏附分子-1(sVCAM-1)、可溶性细胞间黏附分子-1(sICAM-1)的水平,并探讨其临床意义。方法采用酶联免疫吸附试验(ELISA)法,检测30名健康人和60例SLE患者血清sVCAM-1、sICAM-1水平,以分析其与SLE活动性变化关系。结果①SLE患者血清sVCAM-1平均水平为2342ng/ml,显著高于正常人对照组1240ng/ml(P<0.001)。②SLE患者中血清sICAM-1平均水平为802ng/ml,显著高于正常人对照组626ng/ml(P<0.001)。③SLE患者中,血清sVCAM-1水平活动期高于稳定期(P<0.05),sICAM-水平活动期高于稳定期(P<0.05)。④SLE组血清sVCAM-1和sICAM-1水平与SLE病情活动指数(SLEDAI)、抗dsDNA抗体水平及尿蛋白的发生呈正相关,与血清补体C3水平呈负相关。结论sVCAM-1,sICAM-1可能参与SLE发病机制。     

原发性高血压血清sICAM—1和sVCAM—1水平及意义

目的 检测老年早期原发性高血压清可溶性细胞间粘附分子－1(sICAM-1)和可溶性血管间粘附分子－1(sVCAM-1)的水平并分析它们与老年原发性高血压的关系。方法 用ELISA法测定老年原发性高血压患者，正常老年人，正常年轻人血清sICAM-1和sVCAM-1的浓度。结果 老年原发性高血清sICAM-1和sVCAM-1的浓度高于正常老年人和正常年轻人（P＜0．01），另外正常老年人的sICAM-1和sVCAM-1的水平高于正常年轻人（P＜0．01）。结论 老年原发性高血压患者中血清sICAM-1,sVCAM-1的水平明显升高，提示在老年原发性高血压患者中存在内皮细胞结构和功能的改变。我们认为血清sICAM-1,sVCAM-1可作为原发性高血压病发展过程中内皮细胞功能紊乱的一个比较敏感的观察指标。     

急性冠状动脉综合征患者外周血sICAM-1的变化

目的探讨急性冠状动脉综合征(acute coronary syndrome,ACS)患者外周血浆可溶性细胞间粘附分子-1(sICAM-1)水平的变化及其临床意义。方法采用夹心酶联免疫吸附法测定54例ACS,42例稳定型冠心病(SCHD)患者及36例对照组的外周血浆sICAM-1水平。结果ACS组sICAM-1水平显著高于SCHD组和对照组(P<0.01)。SCHD组sICAM-1水平与对照组比较(P<0.05),亦有显著性意义。结论炎症参与了ACS的发病机制,sICAM-1水平的高低与急性冠状动脉综合征病情密切相关,参与了不稳定动脉粥样斑块破裂的病理过程,机体可能通过上调sICAM-1表达而促发ACS。     

Elevated levels of circulating adhesion molecules in patients with active pulmonary tuberculosis

OBJECTIVE: Recent studies have indicated the importance of cell adhesion molecules in the pathogenesis of various inflammatory lung diseases. Our study was designed to determine whether five soluble adhesion molecules including soluble L-, E- and P-selectin (sL-, sE- and sP-selectin), intercellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) in serum reflect the severity of active pulmonary tuberculosis (TB), and whether there is a distinct profile of these soluble molecules in this disease. METHODOLOGY: Using enzyme-linked immunosorbent assays, we measured the serum levels of these five soluble adhesion molecules in 31 patients with active TB and 11 healthy volunteers. RESULTS: Serum levels of sE-selectin, sP-selectin and sICAM-1, but not sL-selectin or sVCAM-1, were significantly higher in patients with active TB than in the control subjects (P < 0.001, each). Significant correlations were detected only between serum levels of sE-selectin and sP-selectin, sE-selectin and sICAM-1, and sP-selectin and sICAM-1. There was a significant correlation between the Gaffky scale result (a scale assessing the number of mycobacteria bacilli present) and all of the above adhesion molecules, except for sL-selectin. Serum levels of sE-selectin, sL-selectin and sICAM-1 also correlated with the CXR radiological score. Higher levels of sL-selectin and sICAM-1 were detected in the serum of patients with radiological cavity formation compared to those without. The ESR, C-reactive protein and circulating neutrophil counts all correlated significantly with sE-selectin, sP-selectin, sICAM-1 and sVCAM-1. CONCLUSION: The results suggest that there is a distinct profile of soluble adhesion molecules in active pulmonary TB and that sE-selectin, sP-selectin, and especially sICAM-1 appear to be the most sensitive clinical measures of disease severity.     

Serum levels of soluble adhesion molecules in stem cell transplantation-related complications.

To assess the involvement of vascular endothelial cell activation and damage in stem cell transplantation (SCT)-related complications, such as acute and chronic GVHD and thrombotic microangiopathy (TMA), we investigated the changes in serum levels of soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) in SCT. The soluble form of intercellular adhesion molecule-1 (sICAM-1) was also analyzed. In patients with acute GVHD (grades II-IV), serum levels of sE-selectin and sICAM-1 increased around onset of GVHD (day 30). While the increase of sE-selectin levels was transient, sICAM-1 levels remained high until day 60. In patients with extensive chronic GVHD, sVCAM-1 as well as sE-selectin levels significantly increased. The appearance of clinical symptoms was preceded by elevations of sVCAM-1 and sE-selectin levels on day 60, and sICAM-1 levels on days 30 and 60. For the analysis of TMA, to exclude the influence of GVHD, serum levels were measured in auto-SCT patients. Around the onset of TMA, sVCAM-1 and sE-selectin levels significantly increased in patients with TMA without an increase of sICAM-1 levels. These findings support the notion that activation and injury of endothelium are commonly involved in the pathogenesis of acute and chronic GVHD and TMA.     

High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia

High serum concentrations of soluble adhesion molecules are present in diabetics, but whether similar levels are present in patients with impaired glucose tolerance (IGT) is unclear. We measured serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin in 128 nondiabetic Japanese subjects. The concentrations of sICAM-1, sVCAM-1, and sE-selectin in IGT patients (n=47) were not different from those in subjects with normal glucose tolerance (NGT; n=81). IGT patients were subdivided into two groups by the results of 75 g OGTT, those with low- (hypoinsulinemia; n=23) or high-insulin (hyperinsulinemia; n=24). The levels of sICAM-1 and sVCAM-1 were not different among NGT and IGT with high-insulin or with low-insulin. However, sE-selectin concentrations were significantly higher in IGT patients with high-insulin than in NGT and IGT with low-insulin (61.1+/-3.4, 47.1+/-1.8 and 43.7+/-3.9 ng/ml, respectively, P<0.001). Adjustment for age and gender did not influence the results. Serum sE-selectin concentrations correlated significantly with the area under the curve of insulin (AUC(insulin)), AUC(glucose), diastolic blood pressure, and triglyceride levels (r=0.35, 0.26, 0.18 and 0.21, respectively), and negatively with HDL-cholesterol levels (r=-0.20). Multiple regression analysis showed that AUC(insulin) was the only independent factor that correlated with sE-selectin levels (P<0.001). Our results indicate that hyperinsulinemia/insulin resistance may be responsible for the elevation of sE-selectin levels.     

Evidence for the regulation of levels of plasma adhesion molecules by proinflammatory cytokines and their soluble receptors in type 1 diabetes

OBJECTIVES: To investigate the regulation of soluble adhesion molecules by tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and relationships with circulating cytokine receptors, in vivo, in type 1 diabetes. DESIGN: Cross-sectional study. SETTING: University hospital diabetes clinic. SUBJECTS: A total of 47 non-nephropathic, Caucasian type 1 diabetics and 39 nondiabetic controls. OUTCOME MEASURES: Plasma levels of TNF-alpha, IL-6, their soluble receptors and adhesion molecules intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin and von Willebrand factor (vWF), and risk factors for cardiovascular disease. RESULTS: Plasma concentrations of IL-6 were elevated in diabetic patients compared with controls [median (interquartiles) 1.28 (0.89-2.65) vs. 0.66 (0.45-1.73) pg mL(-1): P=0.016], and in these patients IL-6 and soluble IL-6 receptor (sIL-6R) levels correlated with concentrations of sICAM-1 (r = 0.41, P = 0.012 and r = 0.31, P = 0.04, respectively). Tumour necrosis factor-alpha soluble receptor-2 (sTN-FRII), but not TNF-alpha or tumour necrosis factor soluble receptor-1 (sTNFRI), was elevated in diabetic subjects (P = 0.027). Plasma TNF-alpha levels correlated with sVCAM-1 (r = 0.39, P = 0.008), triglycerides (r = 0.36, P = 0.02 1) and diastolic blood pressure (r = 0.35; P = 0.024). Both sTNFRI and sTNFRII correlated with blood pressure (r = 0.46, P = 0.002; r = 0.32, P = 0.034) and triglycerides (r = 0.33, P = 0.033; r = 0.29, P = 0.05). In contrast, HDL-cholesterol and triglyceride were related to sE-selectin (r = -0.45 and +0.45; both P < 0.001). Neither sE-selectin nor vWF were related to cytokine concentrations. Finally, both TNF-alpha and sIL-6R correlated sTNFRI and RII (r = 0.44-0.49, P < 0.001). None of these interactions were apparent in control subjects. CONCLUSIONS: (i) IL-6, through effects on sICAM-1, and TNF-alpha via effects on sVCAM-1, may promote vascular adhesion; (ii) plasma levels of TNF-alpha are associated with dyslipidaemia and increased blood pressure, adding to vascular disease risk; (iii) the actions of both cytokines are probably modified by altered production of soluble receptors in diabetic subjects.     

Circulating adhesion molecules in sera of asthmatic children

Infiltration of cells into the lung in asthma is regulated by several expressions of cell adhesion molecules (CAMs) on cells present in the airways, and may play a role in the pathogenesis of bronchial asthma. We sought to evaluate the role of serum concentrations of the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in the control of disease activity in acute asthma. Circulating levels of sICAM-1, sVCAM-1, and sE-selectin in sera from 15 normal control subjects and from 20 allergic asthmatic children with acute exacerbations who had returned to stable condition were determined by using commercially available enzyme-linked immunosorbent assay kits. The mean concentration of serum sICAM-1 levels was significantly higher during an acute exacerbation of asthmatic children than in those with stable asthma (19.41 +/- 10.65 ng/mL vs. 13.46 +/- 5.44 ng/mL; P < 0.001) or in control subjects (9.83 +/- 2.02 ng/mL; P < 0.001). For sVCAM-1 and sE-selectin, the mean serum concentration of sVCAM-1 was slightly higher in children during an acute exacerbation asthma than when stable. However, the differences did not reach statistical significance. The mean serum concentrations of sVCAM-1 and sE-selectin in acute asthma or stable asthma were significantly higher than in control subjects. This study provides further evidence that serum concentrations of sICAM-1, sVCAM-1, and sE-selectin are increased in acute asthma. These findings further confirm that leukocyte endothelial adhesion plays a role in inflammatory airway disease.     

Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure

OBJECTIVES: To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF). BACKGROUND: Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF. METHODS: Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP. RESULTS: Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group. CONCLUSIONS: These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.     

Relationship between insulin resistance, soluble adhesion molecules, and mononuclear cell binding in healthy volunteers.

The relationship between insulin resistance, soluble adhesion molecules E-selectin (sE-selectin), intracellular adhesion molecule-1 (sICAM-1), and vascular adhesion molecule-1 (sVCAM-1), mononuclear cell binding to cultured endothelium, and lipoprotein concentrations were evaluated in 28 healthy, nondiabetic, and normotensive individuals. The mean (+/-SEM) lipid and lipoprotein concentrations were within the normal rage: cholesterol (199 +/- 18 mg/dL); triglyceride (128 +/- 12 mg/dL); low-density cholesterol (127 +/- 8 mg/dL; and high-density cholesterol (47 +/- 3 mg/dL). The results indicated that degree of insulin resistance was significantly correlated with concentrations of sE-selectin (r = 0.54, P < 0.005), sICAM-1 (r = 0.67, P < 0.001), and sVCAM-1 (r = 0.41, P < 0.05). Furthermore, the relationship between insulin resistance and both sE-selectin and sI-CAM-1 remained statistically significant when adjusted for differences in age, gender, body mass index, and all measures of lipoprotein concentrations. Finally, mononuclear cell binding correlated significantly with concentrations of sE-selectin (r = 0.54, P < 0.005) and sICAM-1 (r = 0.47, P < 0.01). These findings raise the possibility that previously described relationships between soluble adhesion molecules in patients with hypertension, type 2 diabetes, and dyslipidemia may be due to the presence of insulin resistance in these clinical syndromes and suggests that insulin resistance may predispose individuals to coronary heart disease by activation of cellular adhesion molecules.