充血性心力衰竭患者血清细胞因子与心功能的关系及阿托伐他汀的干预作用

目的:探讨充血性心力衰竭(CHF)患者血清肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平的变化与心功能的关系及阿托伐他汀对其水平的影响。方法:84例CHF患者被随机分为阿托伐他汀治疗组(42例)和常规治疗组(42例),另选30例健康人作为正常对照组,采用放射免疫方法检测各组治疗前后血清中TNF-α及IL-6的水平,并作心脏超声检查,评估心功能。结果:①84例心功能I~IV级CHF患者血清中TNF-α水平:[(0.52±0.16)μg/L∶(0.64±0.17)μg/L∶(0.79±0.17)μg/L∶(0.88±0.18)μg/L],IL-6[(96.67±17.79)μg/L∶(119.19±25.48)μg/L∶(143.51±26.63)μg/L∶(154.21±23.39)μg/L]随着心功能损害程度加重而显著升高(P0.05);②阿托伐他汀组与常规治疗组治疗后血清TNF-α,IL-6水平均较治疗前明显下降(P均0.05),且阿托伐他汀组较常规治疗组治疗后血清中TNF-α[(0.63±0.21)μg/L∶(0.74±0.19)μg/L],IL-6[(108.87±20.86)μg/L∶(113.92±15.37)μg/L]降低更明显(P0.05);③治疗后阿伐他汀治疗组左室射血分数[(40±6)%∶(36±5)%]、左室收缩末容积指数[(31±6)ml/m2∶(34±5)ml/m2]、左室舒张末容积指数[(47±12)ml/m2∶(51±11)ml/m2]较常规治疗组明显改善(P均0.05)。结论:①充血性心力衰竭患者TNF-,αIL-6水平与心功能状态密切相关;②阿托伐他汀能降低血浆细胞因子(肿瘤坏死因子、白细胞介素-6)水平,改善心脏功能,有益于慢性心力衰竭的治疗。     

心力衰竭患者循环血中肿瘤坏死因子-α、白细胞介素-6、高敏C反应蛋白水平的变化以及阿托伐他汀的干预作用

目的:观察心力衰竭患者血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、高敏C反应蛋白(hs-CRP)水平的变化以及阿托伐他汀的干预作用,探讨阿托伐他汀在心力衰竭治疗中的作用。方法:将60例心力衰竭患者随机分为对照组(常规治疗)和干预组(在常规治疗的基础上加用阿托伐他汀),测定血清中hs-CRP水平以及治疗前和治疗后两周血浆中TNF-α和IL-6水平。结果:心功能NYHAⅣ级患者血浆hs-CRP水平较Ⅲ级明显增高(P＜0.05)。干预组和对照组治疗后血浆TNF-α、IL-6水平均较治疗前明显降低(P＜0.01),且干预组下降更为明显(P＜0.05)。两组治疗后心功能均得到明显改善(P＜0.01)。结论:hs-CRP浓度可作为判断心力衰竭病情程度和预后的预测指标之一。阿托伐他汀对慢性心力衰竭患者可能具有治疗作用。     

阿托伐他汀对CHF患者血清炎症因子水平的影响及意义

目的探讨阿托伐他汀治疗慢性心力衰竭（CHF）的疗效及机制。方法将60例CHF患者随机分为阿托伐他汀组和常规组,两组均予CHF常规治疗,阿托伐他汀组加用阿托伐他汀,疗程均为4周。治疗前后分别采用免疫透射比浊法和放射免疫分析法检测血清血清C反应蛋白（CRP）、IL-6和TNFα-水平,行心脏超声检查测定左室射血分数（LVEF）;检测结果与30例健康体检者（正常组）比较。结果治疗前所有CHF患者血清CRP、IL-6和TNFα-水平均明显高于正常组（P〈0.05）;治疗后均明显降低（P〈0.05）,但阿托伐他汀组较常规组降低更明显（P〈0.05）。与常规组比较阿托伐他汀组LVEF升高更明显（P〈0.05）。结论阿托伐他汀治疗CHF短期效果确切,其机制可能为降低血清炎症因子水平。     

阿托伐他汀短期治疗慢性心力衰竭的临床观察

目的观察短期应用阿托伐他汀对慢性心力衰竭（CHF）患者心功能、血清肿瘤坏死因子-α（TNF-α）和白介素-6（IL-6）水平的影响。方法选择50例CHF患者随机分成治疗组27例和对照组23例。所有CHF患者均给予常规治疗，治疗组在此基础上加用阿托伐他汀10mg／次，1坎／d，晚餐后顿服，治疗4周。治疗前、后分别测量左室射血分数（LVEF）、TNF-α、IL-6和血脂水平。结果两组患者治疗前、后LVEF、TNF-α、IL-6间差异均有显著性意义（P〈0．01）；两组患者治疗前后差异亦均有显著性意义（P〈0．05）；治疗组患者治疗前、后TC、TG、LDL—C间差异均有显著性意义（P〈0．01）；两组患者治疗后TC、LDL—C间差异亦均有显著性意义（P〈0．05）。结论短期应用阿托伐他汀可以降低CHF患者的TNF-α和IL-6水平，改善心功能，其作用机制考虑可能与他汀类药物的非调脂作用有关。     

阿托伐他汀对慢性心力衰竭患者心功能及肿瘤坏死因子-α的影响

目的:探讨阿托伐他汀对慢性心力衰竭患者左室射血分数(LVEF),脑利钠肽(BNP)及肿瘤坏死因子(TNF-α)、核转录因子(NF-κB)活性的影响。方法:将血脂正常的慢性心力衰竭患者50例随机分为对照组(25例)和他汀组(25例)。两组均接受常规治疗(利尿剂、ACEI、或洋地黄、β-受体阻滞剂),他汀组再加用阿托伐他汀(20mg/d)治疗,治疗前及治疗后12周均测LVEF、血清BNP、TNF-α、外周血单个核细胞NF-κB活性。结果:BNP、TNF-α、NF-κB活性与心力衰竭严重程度正相关,治疗12周后,两组TNF-α、BNP、NF-κB活性均下降(P<0.05),LVEF升高(P<0.05),且以他汀组变化更明显,与对照组比较差异有统计学意义(P<0.05)。结论:慢性心力衰竭患者在接受常规治疗的同时,加用阿托伐他汀治疗可明显改善LVEF、降低BNP、TNF-α及NF-κB活性。     

阿托伐他汀对慢性心力衰竭病人心功能及肿瘤坏死因子的影响

目的探讨慢性心力衰竭(CHF)病人肿瘤坏死因子(TNF-α)的变化及阿托伐他汀对其的干预作用。方法将70例CHF病人随机分为阿托伐他汀组和常规治疗组,采用放免法测定CHF病人TNF-α浓度、左室射血分数(LVEF)、左室舒张末内径(LVDd)。结果随着NYHA心功能分级的升高,TNF-α逐渐升高(P0.05);TNF-α与LVEF呈负相关,与LVDd呈正相关;阿托伐他汀组治疗后TNF-α水平显著降低(P0.05),LVEF显著提高(P0.05),LVDd显著降低(P0.05),与常规治疗组治疗后比较差异也有统计学意义(P0.05)。结论在常规治疗的基础上加用阿托伐他汀能进一步降低TNF-α水平,改善心功能。     

阿托伐他汀对血脂正常高血压患者血清TNF-α和IL-6的影响

目的：观察阿托伐他汀对血脂正常高血压患者血清肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的影响。方法：72例血脂正常高血压患者被随机分为常规治疗组（36例,常规降压治疗）与阿托伐他汀组（36例,在常规降压治疗基础上加服阿托伐他汀）,治疗8周。分别于治疗前后检测患者血压及血清TNF-α和IL-6水平。结果：治疗前,两组患者血压及血清TNF-α和IL-6水平比较,差异无显著性（P〉0.05）;治疗后,与常规治疗组比较,阿托伐他汀组患者血压[收缩压（132.45±10.34）mmHg比（128.55±9.22）mmHg,舒张压（88.24±8.66）mmHg比（85.18±8.25）mmHg]及血清TNF-α[（9.43±2.02）ng/L比（7.92±2.13）ng/L]和IL-6[（20.12±3.55）ng/L比（16.65±3.27）ng/L]水平均明显降低（P〈0.05或P〈0.01）。结论：阿托伐他汀对血脂正常高血压患者能协同降压,其机制可能与降低血清肿瘤坏死因子-α和白细胞介素-6水平,抑制炎症反应有关。     

阿托伐他汀对重度慢性心力衰竭病人心功能及相关炎症介质的影响

目的探讨阿托伐他汀对重度慢性心力衰竭病人心功能及高敏C-反应蛋白（hs-CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）等炎症介质的影响。方法64例重度慢性心力衰竭病人（NYHA分级Ⅲ级～Ⅳ级或心脏彩超左室射血分数≤35%）,随机分成两组,对照组30例采用常规治疗。治疗组34例,在常规治疗基础上加用阿托伐他汀20mg,1次/日,口服共10个月。治疗前后检查两组心脏彩超用以评估心功能,采集肘静脉血并分离血清,测定其hs-CRP,IL-6,TNF-α水平。结果治疗10个月后,治疗组病人血浆IL-6,hs-CRP,TNF-α水平降低,且较对照组降低明显（P〈0.05）,同时心功能按NYHA分级治疗组与对照组相比有明显改善（P〈0.01）。结论阿托伐他汀能降低炎症介质（hs-CRP,IL-6,TNF-α）,改善心脏功能,对于重度慢性心力衰竭病人有积极的治疗作用。     

每日口服10mg阿托伐他汀对原发性高血压合并糖耐量减低患者炎症因子水平影响的临床观察

目的 观察每日口服10 mg阿托伐他汀对原发性高血压(EH)合并IGT患者炎症因子水平的影响. 方法 36例EH合并IGT患者(EH+ IGT组)口服阿托伐他汀10 mg,1次/晚.另选择36例体检者作为对照(NC)组.检测两组FPG、2 hPG、胰岛素抵抗指数(HOMA-IR)及血清炎症因子水平的变化. 结果 EH+ IGT组均完成试验.口服10 mg阿托伐他汀治疗8周BP、2 hPG、HOMA-IR、TNF-α及IL-6均下降[BP(159.71±12.25)/(98.67±12.06)们(131.89±10.72)/(81.76±9.03) mm-Hg;2 hPG (8.39±0.65)vs(6.76±1.19)mmol/L;HOMA-IR (3.11±1.95)vs(2.30±1.25);TNF-α(32.11±5.36)vs(24.29±4.57) ng/L;IL-6 (112.37±24.48)vs(70.47±13.30)ng/L] (P＜0.01).结论 每日口服10 mg阿托伐他汀可降低EH合并IGT患者的血清炎症因子水平.     

阿托伐他汀对慢性心力衰竭患者炎症因子及心功能的影响

我们对他汀类药物治疗慢性心力衰竭（CHF）前后血浆炎症因子水平及心功能的变化进行观察,以阐明他汀类药物对慢性心力衰竭的治疗作用及其可能的机制。     

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure

OBJECTIVES: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). BACKGROUND: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. CONCLUSIONS: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.     

Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure

Pro-inflammatory cytokine over-expression may be implicated to the pathogenesis of anemia in chronic heart failure (CHF) through the suppression of bone marrow erythropoiesis. Erythropoietin administration has anti-inflammatory and anti-apoptotic properties in experimental CHF models and improves exercise capacity in anemic CHF patients. The present study investigates the effects of recombinant human erythropoietin analogue darbepoetin-α on circulating pro-inflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with CHF and anemia. Forty-one CHF patients (NYHA class: II–III; left ventricular (LV) ejection fraction (EF) <40%; hemoglobin <12.5 g/dl; serum creatinine <2.5 mg/dl) were randomized to receive either 3-month darbepoietin-α at 1.5 μg/kg every 20 days plus iron orally (n = 21) or placebo plus iron orally (n = 20). LV systolic function, plasma B-type natriuretic peptide (BNP), inflammatory markers (TNF-α, IL-6, CRP), anti-inflammatory cytokine IL-10, endothelial adhesion molecules (soluble ICAM-1 and VCAM-1) and soluble apoptosis mediators (soluble Fas, soluble Fas ligand), and 6-min walking distance were assessed at baseline and 3 months post-treatment. In darbepoetin-α treated patients, plasma BNP (451 (62-2770) from 802 (476-4440) pg/ml, p = 0.002), IL-6 (6.5 ± 4.7 from 10.5 ± 7.8 pg/ml, p = 0.013) and soluble Fas ligand (53.2 ± 16.6 from 59.2 ± 17.9 pg/ml, p = 0.023) decreased significantly, while LVEF (32 ± 6 from 26 ± 6%, p < 0.001), hemoglobin (12.8 ± 1.4 from 10.9 ± 1.0 g/dl, p < 0.001) and 6-min walked distance (274 ± 97 from 201 ± 113 m, p < 0.01) increased significantly. No significant changes were observed in the placebo arm, except for a worsening in 6-min walked distance (p = 0.044). In conclusion, darbepoetin-α reduces circulating pro-inflammatory cytokine IL-6 and apoptotic mediator soluble Fas ligand in CHF patients with anemia, with a parallel improvement of cardiac performance and exercise capacity.     

Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy

Background Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC). Methods Serum levels of tumor necrosis factor-α (TNF-α), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% ± 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo₂max) was also used to evaluate the functional status of patients with IDC. Results Treatment with GH produced a significant reduction in serum levels of TNF-α (8.2 ± 1.2 vs 5.7 ± 1.1 pg/mL, P < .05), sTNF-RI (3.9 ± 0.4 vs 3.2 ± 0.3 ng/mL, P < .05), sTNF-RII (2.6 ± 0.3 vs 2.2 ± 0.2 ng/mL, P < .05), IL-6 (5.5 ± 0.6 vs 4.4 ± 0.4 pg/mL, P = .05), sIL-6R (32.7 ± 3.0 vs 28.2 ± 3.0 ng/mL, P < .05), sFas (4.4 ± 0.8 vs 3.1 ± 0.6 ng/mL, P < .05), and sFasL (34.2 ± 11.7 vs 18.8 ± 7.3 pg/mL, P < .01). A significant improvement was also observed in Vo₂max after the completion of 3 months' treatment with GH (15.0 ± 0.8 vs 17.2 ± 1.0 mL/kg/min, P < .05). Good correlations were found between GH-induced reduction in TNF-α levels and increase in Vo₂max (r = −0.64, P < .05) as well as between GH-induced reduction in sFasL and increase in Vo₂max (r = −0.56, P = .08). Conclusions GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC. (Am Heart J 2002;144:359-64.)     

慢性心力衰竭患者的血清可溶性Fas配体和可溶性Fas受体

目的 分析血清可溶性Fas配体(sFasL)和可溶性Fas受体(sEas)与慢性心力衰竭(CHF)的相关性。方法采用酶联免疫吸附双抗体夹心法检测33例CHF患者(CHF组,心功能Ⅱ-Ⅳ级,NYHA)血清sFasL和sFas浓度,并与18例心功能Ⅰ级(NYHA)组比较。结果 CHF与心功能Ⅰ级间sFasL浓度无显著统计学差异[231.50±84.50(心功能Ⅱ级216.50±96.00,Ⅲ级226.80±85.70,Ⅳ级244.00±73.00)vs217.50±89.00pg/mL,P>0.05]。而CHF组血清sFas浓度显著高于心功能Ⅰ级组[1353.30±507.71(心功能Ⅱ级1154.85±371.20,Ⅲ级1412.88±493.62,Ⅳ级1875.67±806.10)vs983.11±461.26pg/mL,P<0.05]。结论 血清sFasL与CHF无相关性。而血清sFas与CHF存在显著相关性。且sFas浓度增高的程度与CHF的严重程度相平行,sFas浓度增高可能在CHF发病机制中起重要作用。     

尿毒症病人循环单核细胞Fas的表达及血浆FasL水平

目的：慢性肾功能衰竭（肾衰）病人单核细胞功能低下与其凋亡加速有关,兹拟进一步探讨尿毒症病人单核细胞凋亡加速的机制。方法：对7例尿毒症未透析病人和18例液透析（血透）病人进行观察,以15例正常人为对照。采用流式细胞仪检测单核细胞Fas和Fas配基（Fas ligand,FasL）的表达;以ELISA法测定血浆中可溶性FasL（sFasL)的水平。在体外将单核细胞与重组人FasL共同孵育,抽提DNA后用碘化丙啶染色、流式细胞仪检测单核细胞凋亡率,四甲基偶氮唑蓝（MTT）法观察单核细胞存活率。结果：尿毒症未透析病人和血透病人单核细胞Fas的表达较正常人明显上调（P＜0.05）;血透病人的Fas表达水平高于非透析病人（P＜0.05）。正常人和尿毒症病人的单核细胞表面均未检测出FasL表达。正常人血浆中未能检测出sFasL,但尿毒症病人血浆中存在有sFasL;sFasL的水平在尿毒症未透析病人和血透病人之间、血透病人透前与透后之间、以及采用聚砜膜和纤维素膜透析器进行透析的两者之间差异均无显著性（P＞0.05）。单核细胞与重组人FasL在体外共同培养2h后,血透病人单核细胞的凋亡率较正常人明显增高,而其存活率则较正常人明显低下。结论：尿毒症病人单核细胞表面功能Fas表达上调,血浆中存在sFasL,这可能是慢性肾衰病人单核细胞凋亡的原因之一。     

阿托伐他汀钙对慢性心力衰竭患者血浆内皮素及心功能的影响

目的 观察阿托伐他汀钙对慢性心力衰竭患者血清内皮素（ET）及心功能的影响。方法选择98例慢性心力衰竭（NYHA分级Ⅱ～Ⅳ级）患者随机分成2组,治疗组（49例）和对照组（49例）,对照组给予强心、利尿、扩血管等常规治疗,治疗组在此基础上加用阿托伐他汀钙20mg,晚饭后顿服,治疗12月,治疗前后检测血清内皮素-1（ET-1）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL—C）、高密度脂蛋白胆固醇（HDL-C）和左室射血分数（LVEF）情况并进行比较。结果 治疗组与对照组比较,治疗后血清ET-1、TC、TG、LDL．C均有不同程度的降低,左室射血分数（LVEF）则有明显提高。2组比较,差异有统计学意义（P〈0．05或P〈0．01）。结论阿托伐他汀钙能降低血浆ET-1水平,改善心脏功能,有益于慢性充血性心力衰竭的冶疗。     

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: Plasma soluble Fas as a prognostic predictor in patients with congestive heart failure

BACKGROUND: Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). METHODS AND RESULTS: We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. CONCLUSIONS: There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.     

Proinflammatory cytokine activation is linked to apoptotic mediator, soluble Fas level in patients with chronic heart failure

The Fas/Fas Ligand system is a major apoptosis signaling pathway that is up-regulated in patients with chronic heart failure (CHF). Serum soluble Fas (sFas) levels increase in proportion to the CHF severity and may have prognostic value, therefore, sFas is a promising biomarker of heart failure. In this study, we attempted to identify the determinants of sFas levels in patients with CHF. Serum levels of tumor necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 & sTNF-R2), interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein (gp)130, and sFas were measured in 106 patients with CHF and 39 controls. All subjects performed a symptom-limited cycle ergometer exercise test with expired gas analysis. CHF patients had higher levels of TNF-α, sTNF-R1, sTNF-R2, IL-6, and gp130. Serum levels of sFas (controls versus CHF; 2.60 ± 0.88 versus 3.38 ± 1.23 ng/mL, P = 0.0004) were higher in CHF. On univariate analysis, age (P = 0.0003), NYHA functional class (P = 0.0012), peak VO2 (P < 0.0001), plasma norepinephrine (P = 0.0013), log IL-6 (P < 0.0001), log TNF-α (P = 0.0002), log sTNF-R1 (P < 0.0001), and log TNF-R2 (P < 0.0001) were significantly related to log sFas levels. Multivariate analysis showed that age and log IL-6 and log sTNF-R1 levels were independently associated with log sFas levels (overall R = 0.603, P < 0.0001). Serum levels of sFas were increased in patients with CHF, and age and serum IL-6 and sTNF-R1 levels were independent determinants of sFas levels. These data suggest that proinflammatory cytokine activation is linked to the Fas/Fas Ligand system in patients with CHF.     

美托洛尔长期治疗对慢性心力衰竭患者心肌重构和炎性细胞因子的影响

目的:研究β受体阻滞剂美托洛尔对慢性心力衰竭患者心肌重构和血浆肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的影响。方法:选取96例心力衰竭患者,左室射血分数（LVEF）≤45%,心功能（NYHA）ⅡⅣ级,随机分为美托洛尔组和常规治疗组各48例,给于洋地黄、利尿剂、硝酸盐类及血管紧张素转换酶抑制剂（ACEI）治疗,美托洛尔组在此基础上加用美托洛尔6.25 mg,2次/d,并逐渐加量,至最大剂量100 mg,2次/d;或最大耐受剂量。治疗6月后,观察比较两组治疗前后心率、血压、心功能、心胸比率、超声心动图变化,用双抗体夹心ELISA法测定美托洛尔组治疗前后血浆TNF-α、IL-1β和IL-6的变化。结果:美托洛尔平均剂量127 mg/d,美托洛尔组和常规治疗组治疗后心功能改善（3.1±0.7vs1.5±0.6,P<0.01;3.0±0.7vs2.0±0.4,P<0.01）、LVEF提高[（34.3±7.8）%vs（46.1±10.5）%,P<0.01;（36.2±5.9）%vs（39.9±5.5）%,P<0.01]。美托洛尔组左室舒张末内径（LVEDD）比治疗前显著减小（68.0±10.6 mmvs63.6±10.4 mm,P<0.01）、心胸比率降低（0.61±0.08vs0.58±0.07,P<0.05）;美托洛尔组血浆TNF-1、IL-1β和IL-6显著降低（53±23vs35±14;32±12vs20±4;50±21vs21±11 pg/m l,P<0.01）。结论:在慢性心力衰竭常规治疗基础上加用β1受体阻滞剂美托洛尔安全有效,可以改善心功能,逆转心肌重构,降低血浆主要细胞因子水平。     

慢性心力衰竭患者炎性细胞因子的变化及作用

目的探讨致炎细胞因子白细胞介素1(IL-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)和抗炎细胞因子白细胞介素10(IL-10)在慢性心力衰竭发生发展中的变化及作用。方法入选心力衰竭患者150例和健康对照50名,采用酶联免疫吸附法检测血清IL-1、IL-6、IL-10、TNF-α和IFN-γ的水平。结果心力衰竭组患者血清IL-1、IL-6、IL-10、TNF-α和IFN-γ的水平显著高于对照组(P<0.05或P<0.01),且随着纽约心功能分级(NYHA)的增加而升高,并与左心室射血分数(LVEF)呈负相关(r=-0.586、-0.454、-0.521、-0.514、-0.502,均为P<0.01),与左心室舒张末容积(LVEDV)呈正相关(r=0.603、0.45、0.542、0.519、0.438,均为P<0.01);IL-1、IL-6、TNF-α、IFN-γ总和与IL-10的比值:NYHAⅢ级和Ⅳ级患者高于对照组(P<0.05或P<0.01),NYHAⅣ级患者高于Ⅲ级和Ⅱ级患者(P<0.05),NYHAⅢ级患者高于Ⅱ级患者(P<0.05),但NYHAⅡ级患者与对照组间差异无统计学意义(P>0.05);冠心病心力衰竭和扩张型心肌病心力衰竭患者的IL-1、IL-6、IL-10、TNF-α和IFN-γ水平比较,差异无统计学意义(P>0.05)。结论心力衰竭患者致炎细胞因子和抗炎细胞因子均增高,但抗炎因子增加相对不足,炎症反应随着心力衰竭程度加重而加重,与心功能状态有相关性,与病因无显著相关性,细胞因子在心力衰竭的发生发展中起着重要的作用。