急性冠脉综合征患者血小板CD40L与血清中性粒细胞的相关性研究

目的:探讨急性冠脉综合征患者血小板CD40L表达与中性粒细胞的相关性.方法:收集在本院住的急性冠脉综合征患者87例,其中不稳定心绞痛72例,急性心肌梗死15例.采用流式细胞技术检测血小板CD40L的表达,采用Pearson相关分析法研究血小板CD40L与血清白细胞和中性粒细胞数的相关性.结果:急性心肌梗死组患者血小板CD40L水平(3.96±2.36)显著高于不稳定心绞痛组(3.77±2.53,P＜0.05).急性冠脉综合征患者血小板CD40L表达与血清白细胞计数、中性粒细胞计数均呈正相关,(相关系数r分别为0.466和0.519,均P＜0.05):结论:急性冠脉综合征患者血小板CD40L表达与中性粒细胞计数呈正相关.     

氯吡格雷对冠心病患者PCI前后血小板膜CD40L的影响

目的探讨冠心病患者血小板膜CD40L在PCI术前后的变化及其临床意义。方法选择30例经冠状动脉造影确诊为冠心病的患者，男女不限，平均年龄56±9岁，无抗血小板聚集药物禁忌症，接受规范的抗心绞痛治疗，术前给予氯吡格雷75mg／d，行冠脉内介入治疗（PCI），采用流式细胞仪测定患者PCI术前及术后6小时活化血小板CD40L的表达率。结果30例患者PCI术前血小板CD40L的表达率水平为3．73±2．15，术后6小时为2．46±0．90，术后6小时血小板CD40L的表达较术前显著降低（P〈0．01）。结论氯吡格雷对冠心病患者PCI术后早期血小板膜CD40L有显著影响，可有效抑制血小板活化，预防血栓栓塞事件发生。     

急性冠脉综合征患者外周血CD40L表达增高

目的检测急性冠脉综合征(ACS)患者CD4 T细胞CD40L的表达率、血清可溶性CD40配体(sCD40L)的水平,探讨CD40/CD40L在ACS发病中的作用及可能途径。方法ACS患者42例,包括稳定型心绞痛(SAP)12例、不稳定型心绞痛(UAP)14例、急性心肌梗死(AMI)16例;健康对照者13例。流式细胞分析术检测CD4 T细胞表达CD40L的阳性细胞率,ELISA法检测血清sCD40L水平。结果AMI、UAP、SAP、对照组CD4 T细胞中表达CD40L的阳性细胞率分别为(8.67±3.31)%、(3.24±1.13)%、(2.29±1.93)%、(0.57±0.19)%,AMI组显著高于其他三组(P均<0.05),UAP组亦显著高于对照组(P<0.05);四组血清sCD40L水平分别为(14.53±8.08)ng/mL、(8.06±6.96)ng/mL、(7.37±3.59)ng/mL、(4.45±1.48)ng/mL,AMI组显著高于其他三组(P均<0.05)。结论ACS患者CD4 T细胞CD40L的表达率和血清sCD40L水平增高,在ACS发病过程中起重要作用;CD40L和sCD40L有望作为冠心病危险性的预测因子。     

血小板CD40L的免疫调节作用

血小板CD40L与其受体CD40间的相互作用构成了体液免疫和细胞免疫应答间的桥梁,且两者的相互作用涉及到许多炎症反应过程,包括血小板-淋巴细胞的相互作用.在血小板、T细胞和B细胞间的同型或异型相互作用中,CD40/CD40L是一种重要的调节机制;血小板和中性粒细胞通过CD40L-CD40途径的相互作用,最终导致血小板和...     

替罗非班对急性冠脉综合征患者血小板CD40L及血清MMP-9水平的影响

目的观察盐酸替罗非班对急性冠脉综合征（ACS）患者血小板CD40L表达、血清MMP-9水平的影响。方法ACS患者60例,随机分为试验组与对照组,应用流式细胞术及明胶酶谱法分别检测药物治疗前及48小时后血小板CIMOL及血清MMP-9水平。结果试验组血小板CIMOL及血清MMP-9升高水平较对照组低（P〈0．05）。结论替罗非班可以减弱ACS患者血小板CD40L、血清MMP-9表达,对预防ACS患者进一步的心脏缺血事件有积极作用。     

急性冠状动脉综合征全血CD40L和CD64检测分析

目的 分析急性冠状动脉综合征患者全血CD40L和CD64检测结果.方法 分别应用流式细胞术技术对30例AMI组,30例UAP组及20例健康对照组的全血CD40L和CD64及其T淋巴细胞亚群检测.结果 CD40L,CD64在AMI组,UAP组与健康对照组比较中明显高于健康对照组,而T淋巴细胞亚群变化不显著.AMI组CD40L,CD64明显高于UAP组,而UAP组明显高于健康对照组,差异有统计学意义(P<0.05).结论 全血CD40L和CD64量的升高可能与急性冠状动脉综合征的发生有关,可能是动脉粥样硬化斑块不稳定的敏感标志.     

CD40-CD40L与急性冠脉综合征

大量基础与临床的研究资料均显示，不稳定性粥样斑块破裂、斑块中致凝血物质与血液直接接触和组织因子大量释放，导致冠脉急性血栓形成，是引发急性冠脉综合征(ACS)的真正罪魁祸首。不稳定性斑块的破裂是ACS发生的病理基础，免疫与炎症反应在ACS的发生、发展过程中亦起着重要的作用。CD40/CD40L作为免疫及炎症反应中重要的信号转导系统，在动脉粥样硬化及急性冠脉综合征的发病机制中起着极为关键的作用，它几乎贯穿动脉粥样硬化发生发展乃至斑块破裂继发血栓形成的全过程。     

海藻糖对保存血小板分泌可溶性CD40L抑制作用的研究

目的了解室温(22±2℃,水平震荡)储存单采血小板分泌可溶性CD40L(sCD40L)的浓度变化及在单采血小板中添加海藻糖对血小板分泌sCD40L的影响。方法取20份单采血小板浓缩液,用ELISA法检测sCD40L浓度,观察室温储存的单采血小板分泌sCD40L的水平。然后分别用0、10、20、30、40、50、60 mg/m l 7种不同浓度的海藻糖缓冲液负载血小板,在室温下行观察性研究海藻糖抑制sCD40L分泌的剂量效应,选取合适的海藻糖负载浓度,进而对比研究合适的海藻糖浓度对抑制血小板分泌sCD40L的效应。结果单采血小板在保存期内,随保存时间延长sCD40L浓度逐渐增高,至d 5时与d 0比较差异有显著性,海藻糖对抑制血小板分泌sCD40L呈剂量依赖性及时间依赖性,海藻糖的负载浓度越高抑制血小板分泌sCD40L的作用越强。合适的海藻糖的负载浓度为50 mg/m l,其抑制作用随保存时间延长有逐渐减弱的趋势,但差异无统计学意义。结论单采血小板在室温储存期间不断分泌sCD40L,海藻糖可作为保护剂有效抑制血小板分泌sCD40L,这为临床预防和解决血小板输注副反应提供实验数据及新的思路和策略。     

欣维宁对急性心肌梗死患者PCI术后血小板CD40L及血清MMP-2表达水平的影响

目的探讨急性心梗（AMI）患者PCI术前、术后血小板表面CD40L及血清中MMP-2表达的变化，观察欣维宁（盐酸替罗非班）对PCI术后血小板CIMOL表达、MMP-2水平的影响。方法急性心梗患者30例，均于发病后6小时内行急诊介入治疗，随机分为试验组与对照组，应用流式细胞术及明胶酶谱法分别检测PCI术前后血小板CD40L表达、血清MMP-2水平。结果1试验组与对照组PCI术后血小板表面CD40L及血清MMP-2水平均较术前升高（P＜0．001）。2试验组血小板CD40L及血清MMP-2升高水平较对照组低（P＜0．05）。结论欣维宁可以减少AMI患者PCI术后血小板CD40L、血清MMP-2表达，对预防PCI术后血栓栓塞并发症有积极作用。     

急性冠脉综合征患者替罗非班治疗后过氧化物酶体增生激活型受体γ与CD40/CD40L通路表达的变化

目的观察急性冠脉综合征(ACS)患者替罗非班治疗后过氧化物酶体增生激活型受体γ( PPARγ)与CD40/CD40L通路表达的变化。 方法选取2016年12月至2017年7月邯郸市第一医院心内科ACS患者120例,随机数字表法分成4组,为常规治疗组和常规治疗＋替罗非班12 h、24 h、36 h组,每组30人,进行随机对照研究。替罗非班组经皮冠状动脉介入治疗(PCI)术12 h后、24 h后、36 h后分别抽取患者血液,酶联免疫吸附法(ELISA)测定PPARγ与CD40、CD40L蛋白水平的表达,反转录-聚合酶链反应(RT-PCR)方法检测PPARγ与CD40、CD40L mRNA表达。 结果与常规治疗组比较,替罗非班12 h、24 h、36 h组CD40与CD40L蛋白水平表达逐渐降低,CD40水平分别为(0.86±0.08)μg/L、(0.46±0.05)μg/L、(0.40±0.05)μg/L;CD40L水平分别为(0.92±0.04)μg/L、(0.54±0.04)μg/L和(0.40±0.05)μg/L,均差异有统计学意义(F＝1 977.39,5 071.39;均P<0.01);PPARγ蛋白表达水平上升,分别为(0.94±0.04)μg/L、(1.40±0.01)μg/L和(1.48±0.01)μg/L,差异有统计学意义(F＝4 719.81,P<0.01);替罗非班组CD40和CD40L mRNA表达逐渐降低,分别为0.98±0.07、0.50±0.02、0.41±0.01和1.02±0.06、0.50±0.02、0.40±0.01,均差异有统计学意义(F＝5 781.52,5 935.29;均P<0.01);PPARγ mRNA表达升高,分别为0.74±0.04、1.31±0.01和1.49±0.01,差异有统计学意义(F＝4 683.59,P<0.01)。 结论替罗非班能上调PPARγ表达,同时抑制CD40/CD40L通路的激活,具有抑制炎症、稳定粥样斑块作用。     

Increased plasma concentrations of soluble CD40 ligand in acute coronary syndrome depend on in vitro platelet activation

BACKGROUND: Soluble CD40 ligand (sCD40L) was suggested as a novel biomarker of cardiovascular risk. We examined the effect of preanalytical variation on the measurement of sCD40L concentration. METHODS: From healthy control individuals (n = 20) and patients with acute coronary syndrome (ACS) (n = 20) or sepsis (n = 20), we obtained blood drawn into 5 tubes containing citrate or a mixture of citrate, theophylline, adenosine, and dipyridamole (CTAD). The tubes were incubated for 30 min at room temperature or 0 degrees C before a single or double centrifugation (15 min, 2500 g) at room temperature or 4 degrees C, respectively. sCD40L, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4) concentrations were measured using immunoassays. RESULTS: Concentrations of sCD40L were very low in all CTAD and citrated samples maintained at 0 degrees C (median < or = 0.076 microg/L). Although increased betaTG and PF4 confirmed disease-related in vivo platelet activation, sCD40L was not higher in patients than in controls. In contrast, if the samples were processed at room temperature, sCD40L was significantly higher in ACS patients than in controls (P <0.02 in CTAD and citrated plasma at room temperature). Moreover, the betaTG:PF4 ratio decreased in patient but not control CTAD samples, suggesting a greater susceptibility of patient platelets to in vitro activation. CONCLUSIONS: Increased sCD40L concentrations resulted from in vitro platelet activation during sample preparation. Disease-related in vivo activation did not contribute to sCD40L concentrations in plasma. Therefore, published studies of sCD40L demand cautious interpretation, because their preanalytical conditions were not standardized.     

The clinical implications of increased OX40 ligand expression in patients with acute coronary syndrome

BACKGROUND: Increasing evidence show that OX40 ligand (OX40L), also known as tumor necrosis factor superfamily member 4 (TNFSF4), plays an important role in the pathogenesis of atherosclerosis. We investigated whether expression levels of soluble OX40L in serum and of membrane OX40L on platelets were related to serum concentrations of matrix metalloproteinases (MMPs) and stability of coronary atherosclerotic plaque in patients with acute coronary syndrome (ACS). METHODS: We included healthy controls (n=30), patients with stable angina (SA) (n=40) and patients with ACS, including unstable angina (UA) (n=70) and acute myocardial infarction (AMI) (n=40). The expression of OX40L on platelets (pOX40L) was analyzed with flow cytometry whereas serum concentrations of soluble OX40L (sOX40L), MMP-9 and MMP-3 were determined with ELISA. All coronary stenoses with >/=30% diameter reduction were assessed by angiographic coronary stenosis morphology. RESULTS: The expression of OX40L on platelets were significantly higher in patients with ACS (61.5+/-11.5) compared with healthy controls (28.9+/-7.4) or with the group of patients with SA (31.2+/-8.1) (mean fluorescence intensity+/-SD) (p<0.001). Similarly, we observed higher sOX40L concentrations in patients with ACS (34.6+/-9.3) compared with controls (10.2+/-4.7) or patients with SA (11.4+/-5.8) (ng/ml+/-SD) (p<0.001). Serum MMP-3 and MMP-9 levels in patients were two times greater than those in the control group. A positive correlation was observed between OX40L expression on platelets and MMP-9 and MMP-3 serum concentrations. OX40L expression on platelets were furthermore correlated with soluble OX40L in serum and with complex coronary stenoses (r1=0.61, r2=0.57, p<0.001). CONCLUSION: Patients with ACS show increased OX40L system (pOX40L and sOX40L) expression which may create a proinflammatory milieu for aggravating the development of atherosclerosis, and may be a valuable marker for predicting the severity of ACS.     

Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome

BACKGROUND: Increasing evidence indicates that the CD40-CD40L interaction plays a pivotal role in the inflammatory regulation of atherosclerosis. Adhesion molecules especially the vascular adhesion molecules also play an important role in the pathogenesis of atherosclerosis which act as markers of inflammation. These inflammatory factors render vulnerability to the atherosclerotic plaque by triggering the fissure, rupture, and subsequent thrombosis, leading to the clinical scenario of unstable angina and acute myocardial infarction. METHODS: The difference of sCD40L concentration in different subtype of coronary heart disease and its relationship with vascular adhesion molecules was investigated. Enzyme-linked Immunosorbent Assay (EIA) was used to measure the serum sCD40L, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1). RESULTS: The sCD40L concentration was significantly higher in patients with acute coronary syndrome (ACS) (3.17+/-2.84 ng/ml) than in controls (1.19+/-1.05 ng/ml, p<0.01) and in patients with stable coronary heart disease (1.61+/-1.46 ng/ml, p<0.05). The sCD40L concentration was positively correlated with sICAM-1 (r=0.413, p<0.01), triglycerides (TG) (r=0.23, p<0.05), apoB (r=0.248, p<0.05), and HDL-cholesterol (r=-0.253, p<0.05). CONCLUSIONS: The sCD40L concentration was increased in acute coronary syndrome, suggesting the possible relation of CD40L to the pathogenesis. The serum CD40L concentration was positively correlated with adhesion molecule and was negatively associated with serum high-density lipoprotein cholesterol (HDL-C).     

辛伐他汀在急性冠脉综合征中的应用

目的　观察辛伐他汀在治疗急性冠脉综合征(ACS)中的治疗作用。方法　将10 0例ACS患者随机分为两组:辛伐他汀治疗组(辛伐他汀+常规治疗,即治疗组)和常规治疗组(对照组) ,每组5 0例,观察用药前后血脂变化及主要心血管事件发生情况。结果　对照组治疗前后血脂无显著改变(P >0 .0 5 )。治疗组经辛伐他汀治疗10周后,血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL C)水平明显降低,高密度脂蛋白胆固醇(HDL- C)水平略有上升,明显降低心血管事件发生率(χ2 =4 .6 8,P <0 .0 5 ) ,治疗前后肝肾功能无明显变化。结论　他汀类药物治疗ACS能显著改善临床症状,延缓动脉硬化的发展,降低ACS早期临床事件发生率。     

辛伐他汀对急性冠脉综合征患者颈动脉粥样硬化的影响

目的：探讨辛伐他汀对急性冠脉综合征患者颈动脉粥样硬化的影响及其机制。方法：80例急性冠脉综合征患者随机分成辛伐他汀20 mg组（40例）和辛伐他汀40 mg组（40例）,于治疗前及治疗6个月后分别测定血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）及高密度脂蛋白胆固醇（HDL-C）水平,并超声检测颈动脉内-中膜厚度（IMT）及颈动脉斑块面积。结果：两组治疗后TC、TG、LDL-C水平均明显降低（P〈0.01）,HDL-C明显升高（P〈0.01）;而辛伐他汀40 mg组较20 mg组作用更为明显（P〈0.05）。治疗6个月后IMT及颈动脉斑块面积明显缩小（P〈0.01）,且辛伐他汀40 mg组作用更显著（P〈0.01）。结论：辛伐他汀对急性冠脉综合征患者颈动脉粥样硬化斑块具有延缓和稳定作用。     

不同剂量辛伐他汀早期干预对非ST抬高型急性冠脉综合征sCD40L水平的影响

目的：探讨不同剂量辛伐他汀早期干预治疗对非ST抬高型急性冠脉综合征患者sCD40L水平的影响。方法：60例非ST抬高型急性冠脉综合征患者随机分为3组：A组为常规治疗组（20例）予以常规治疗但不用降脂药物；B组（20例）为20mg辛伐他汀治疗组；C组为40mg辛伐他汀治疗组（20例）；20例稳定性心绞痛患者为对照组。60例非ST抬高型急性冠脉综合征患者在治疗2周前后分别测定血清sCD40L及血脂水平。结果：60例非ST抬高型急性冠脉综合征患者的血清sCD40L水平明显高于稳定性冠心病患者（P＜0．05），B、C组治疗2周后血清sCD40L平均有明显下降（P〈0.05），而以C组作用更明显。结论：非ST抬高型急性冠脉综合征患者血清sCD40L水平增高，早期辛伐他汀治疗可降低非ST抬高型急性冠脉综合征患者的血清sCD40L水平，且呈剂量依赖性。早期他汀类药物强化治疗可能使非ST抬高型急性冠脉综合征患者获益更大。     

CD40-1C/T基因多态性与急性冠脉综合征易感性的研究

目的 探讨CD40基因-1C/T单核苷酸多态性位点(SNP)与急性冠脉综合征(ACS)易感相关性及血小板表达CD40的关系.方法 研究对象来自江苏大学附属医院心内科2007年7月至2008年11月住院患者.ACS患者210例,SA患者189例,对照组163例.ACS的诊断:(1)心绞痛或胸闷或心电图改变;(2)肌钙蛋白I升高;(3)冠脉造影至少一支冠脉血管直径狭窄≥50%.稳定型心绞痛:心绞痛稳定发作3个月以上.所有入选者均行冠脉造影.排除患有感染、肿瘤及肝肾疾病.采用聚合酶链反应-限制性片段长度多态性(PCR-RELP)检测CD40基因多态性并测序鉴定,流式细胞术检测血小板表达CD40水平.等位基因频率及遗传平衡采用x~2检验.结果 ACS组CC基因型频率(31%)及C等位基因频率(57.9%)明显高于SA组(15.9%,43.1%)及对照组(16.0%,42.6%),在SA组与对照组差异无统计学意义(X~2=0.053,P=0.974;X~2=0.017,P=0.897).各组C等位基因携带者血小板表达CD40水平明显增高(P<0.0001).结论 CD40基因-1C/T SNP与ACS相关,C等位基因增加ACS患病风险.     

The effect of elevated serum soluble CD40 ligand on the prognostic value in patients with acute coronary syndromes

BACKGROUND: Increasing evidence shows that high expression of CD40L plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. We evaluated the clinical predictive value of increased serum soluble CD40 ligand (CD40L) in patients with acute coronary syndromes (ACS) and acute chest pain. METHODS: Serum levels of soluble CD40 ligand were measured by ELISA in 128 patients with ACS and in 68 patients with acute chest pain. Platelet activation was assessed by flow cytometry. RESULTS: The levels of soluble CD40 ligand were increased in 57.8% patients with ACS (>8.0 ng/ml) and in 35 patients with acute chest pain (>8.0 ng/ml), respectively. The level of soluble CD40 ligand was slightly correlated with measured levels of troponin T (r=0.21, p<0.05), and the increased soluble CD40L levels (>8.0 ng/ml) were associated with higher risk for AMI, sudden death and recurrent angina. Patients with elevated serum levels of sCD40L and cTnT showed a significantly increased risk of major adverse cardiovascular events (including AMI, sudden death and recurrent angina) in the two groups during 30 days and 6 months of follow-up. CONCLUSION: In patients with unstable coronary artery disease, elevation of serum soluble CD40L levels indicated an independent increased risk of major adverse cardiovascular events.