高脂血症、高血压患者血小板CD40L及可溶性sCD40L表达差异的研究

目的探讨单纯混合性高脂血症、单纯高血压患者血小板CD40L及sCD40L的表达情况及其可能机制。方法单纯混合性高脂血症组、单纯高血压组、对照组各按严格入选标准选取15例,同条件下流式法检测血小板CD40L的表达,ELISA法检测血浆sCD40L的浓度,观察各组间两指标的表达情况及相互关系。结果单纯高脂血症组血小板CD40L的表达明显高于对照组和单纯高血压组(P<0.01),sCD40L的血浆浓度也明显高于对照组和单纯高血压组(P<0.05),而两指标在单纯高血压组与对照组间的差异均无显著统计学意义(P>0.05)。结论单纯混合性高脂血症患者血小板CD40L及血浆sCD40L的表达明显升高,可能参与了冠状动脉粥样硬化的发生和发展。     

血小板数量与血清sCD40L浓度变化的关系

最近,我们发现苏州地区健康人群血小板参考范围比目前的正常参考范围偏低,而其功能未见异常。CD40L是近年来证实为活化的血小板表达的Ⅱ型膜传递蛋白分子,活化后血小板性CD40L以可溶性CD40L(sCD40L)方式释放进入血液。血小板偏低的健康人和血小板生成低下的再生障碍性贫血(再障)病人,其sCD40L浓度变化特点尚未见报道。本文采用双抗体夹心(ELISA)法对健康人血小板低值组,健康人血小板高值组和再障患者血清sCD40L进行了检测,结果如下。     

sCD40L在大动脉粥样硬化性卒中患者中的表达及其意义

目的 探讨可溶性CD40配体(sCD40L)在大动脉粥样硬化性卒中(LAA)患者的表达及意义.方法 用ELISA法连续测定29例LAA患者(A组)和11例健康体检者(B组)血浆sCD40L、血小板膜蛋白140(GMP-140)和白细胞介素6(IL-6)含量.结果 与B组比较,A组血小板GMP-140含量增高[(43.78±16.61)ng/ml vs.(9.42±2.96)ng/ml](P＜0.01),sCD40L和ID6亦明显增高[(8.36±4.30)ng/ml vs.(3.52±1.69)ng/ml和(55.59±18.20)pg/ml vs.(30.33±7.45)pg/ml](P＜0.01).A组患者sCD40L与GMP-140水平、sCD40L与IL-6水平、GMP-140与IL-6水平均呈正相关.结论 LAA患者血循环中sCD40L含量升高,提示血小板源性CD40L是炎症、动脉粥样硬化斑块不稳定和血栓形成的一个重要介质.循环中sCD40L升高可作为血小板活化、不稳定动脉粥样斑块发展为缺血性卒中的标志物.     

2型糖尿病高尿酸血症与胰岛素抵抗及动脉粥样硬化的关系

目的了解2型糖尿病高尿酸血症和胰岛素抵抗及动脉粥样硬化的关系。方法采用高敏感B型超声测定107例2型糖尿病患者颈动脉内膜—中膜厚度(IMT)作为亚临床动脉粥样硬化的指标,同时测定血尿酸、胰岛素敏感指数和胰岛素抵抗指数。结果2型糖尿病尿酸升高组体重指数、收缩压、舒张压、空腹胰岛素、负荷后2小时胰岛素、胰岛素抵抗指数明显高于尿酸正常组,高密度脂蛋白胆固醇和胰岛素敏感指数明显低于尿酸正常组;尿酸升高组颈动脉平均IMT、最大IMT和大血管病变发生率比尿酸正常组明显增厚;血尿酸与颈动脉IMT明显相关,但校正了年龄、体重、血压、血脂等因素后血尿酸与颈动脉IMT相关不明显,血尿酸主要与体重指数和胰岛素抵抗指数独立相关。结论高尿酸血症是胰岛素抵抗综合征的一个重要方面,血尿酸不是2型糖尿病大血管病变和动脉粥样硬化的独立危险因素,尿酸与大血管病变和动脉粥样硬化的关系归因于尿酸和其他危险因素存在关联,但尿酸可以作为2型糖尿病动脉粥样硬化的重要标志物。     

CD40-CD40L系统对主动脉粥样硬化兔血浆黏附分子水平的影响

目的探讨CD40-CD40配体系统(CD40-CD40L)对不同因素致动脉粥样硬化形成的血浆黏附分子影响。方法 40只实验兔随机分为5组,每组8只。A组(正常对照组):普通颗粒饲料喂饲;B组(高脂模型组):高脂饲料喂饲;C组(高脂模型CD40阻断组):高脂饲料喂饲同时给予抗CD40配体抗体0.5ml(250μg),腹腔注射,每周两次;D组(免疫刺激组):应用肺炎衣原体感染制备动脉硬化模型;E组(免疫刺激CD40阻断组):制备模型的同时给予抗CD40配体抗体0.5ml(250μg),腹腔注射,每周两次;实验共16周。实验结束后,检查如下指标:①ELISA法检测sCD40L、sVCAM-1、sICAM-1。斑块/内膜面积比。16周末获取标本检测分析。结果 B、C、D、E组与A组比较sCD40LsVCAM-1、sICAM-1水平升高(P<0.01)。C、E组与B、D组比较sCD40L、sVCAM-1、sICAM-1水平降低(P<0.01)。结论通过高脂饮食、免疫刺激可引起实验兔sCD40L、sVCAM-1、sICAM-1水平升高,阻断CD40-CD40L,可降低实验兔sCD40L、sVCAM-1、sICAM-1水平,从而抑制炎症反应、延缓动脉粥样硬化进展。     

2型糖尿病患者促甲状腺激素同型半胱氨酸与颈动脉内中膜厚度的相关性

<正>糖尿病大血管病变主要指糖尿病导致或合并的冠心病、脑血管病及外周血管病,是由多种因素相互作用的结果。颈动脉内中膜厚度(IMT)增厚是诊断颈动脉粥样硬化及反映糖尿病大血管病变的指标。大量研究表明,糖尿病患者血清高同型半胱氨酸(Hcy)水平是糖尿病慢性并发症、动脉粥样硬化和冠心病的一个独立危险因素。相关研究显示,促甲腺激素(TSH)升高可能从与血脂代谢、血管内皮、凝血功能等多方面影响动脉粥样硬化的形成、发展和预后[1]。2型糖尿病患者     

慢性心力衰竭患者体内CD40L高表达的临床意义

目的 探讨慢性心力衰竭(CHF)患者体内CD40配体(CD40L)表达的临床意义.方法 CHF患者140例及正常对照组30例,采用间接免疫荧光流式细胞术和ELISA法检测血小板表达CD40L及血清可溶性CD40L(sCD40L)水平,脑钠肽(BNP)采用放射性免疫法检测.结果 CHF患者血小板表达CD40L[(39.4±13.7)MFI]及血清sCD40L[(23.8±8.7)ng/ml]水平均明显增高(P＜0.01),且CHF患者血小板表达CD40L及血清sCD40L水平与纽约心功能分级(NYHA)、左室射血分数(LVEF)及BNP水平显著正相关(P＜0.01).结论 CD40L表达水平的增高可能参与了CHF的发生、发展.     

2型糖尿病患者血尿酸水平与颈动脉内中膜厚度的相关性研究

目的探讨血尿酸水平与2型糖尿病合并颈动脉内中膜厚度的关系。方法对198例糖尿病病程在5年之内的2型糖尿病患者和52名对照者测定血尿酸水平,对糖尿病患者测定颈动脉内中膜厚度(IMT),并以IMT≥0.9 mm分为糖尿病无内中膜厚度增厚组和糖尿病合并内中膜厚度增厚组。结果糖尿病合并颈动脉内中膜厚度增厚组的尿酸水平较糖尿病无颈动脉内中膜厚度增厚组显著增高[(485±38)μmol/Lvs(433±27)μmol/L,P<0.05],高尿酸血症的发生率亦显著高于糖尿病无内中膜增厚组和对照组(P<0.05)。结论高尿酸血症与2型糖尿病合并颈动脉内中膜厚度有关,并且是糖尿病早期大血管病变的危险因素。     

阿托伐他汀对颈动脉粥样硬化患者血清sCD40L水平的影响

目的探讨阿托伐他汀对颈动脉粥样硬化患者血清sCD40L浓度的影响,并探究其阻断CD40/CD40L信号途径的作用。方法选取颈动脉粥样硬化患者80例,随机分为对照组和试验组,每组40例。分别给予饮食控制和阿托伐他汀治疗,随访12周。治疗前、治疗后第4周、第12周检测血清sCD40L、血总胆固醇、甘油三酯、低密度脂蛋白。结果治疗组治疗后第4周、第12周所测指标浓度水平显著低于治疗前水平(P<0.05),且第12周指标血清浓度低于第4周血清浓度(P<0.05)。而对照组以上指标无明显变化。尚不能认为低密度脂蛋白水平异常对于阿托伐他汀的降血清sCD40L浓度作用有影响。结论阿托伐他汀能够显著降低颈动脉粥样硬化患者血清sCD40L浓度,具有除调脂作用外抗动脉粥样硬化的作用。     

可溶性CD40L与急性冠脉综合征的临床研究

目的 探讨急性冠状动脉综合征(ACS)患者血清可溶性CD40L(sCD40L)水平变化的临床意义.方法 应用酶联免疫测定法(ELISA)对正常对照组40例,不稳定心绞痛(UA)42例,急性心肌梗塞(AMI)13例,外周血sCD40L水平进行检测.结果 ACS组血清sCD40L水平明显高于对照组(P<0.01),AMI组血清CD40L水平又高于UA组,差异有显著性(P<0.05).随访期ACS sCD40L增高组心血管事件发生率明显高于正常组(P<0.01).结论 sCD40L水平升高可能与急性冠状动脉综合征的发生有关,是动脉粥样硬化斑块不稳定的标志.     

Relationship between upregulation of CD40 system and restenosis in patients after percutaneous coronary intervention

AIM: To investigate whether the increasing CD40-CD40 ligand system is related to restenosis in patients after percutaneous coronary intervention (PCI). METHODS: Twenty normal controls and 120 patients with PCI were investigated. The expression of CD40 and the CD40 ligand (CD40L) on platelets was analyzed by indirectimmunofluorescence flow cytometry. The serum level of soluble CD40L (sCD40L) and C-reactive protein (CRP) was determined by commercially available enzyme linked immunosorbent assay. Restenosis was observed in 120 patients within a 6 month follow-up period after PCI surgery. RESULTS: Restenosis occurred in 29 patients (24.2%). Patients who developed restenosis showed higher levels of CD40-CD40L system compared with non-restenotic patients before PCI. All restenotic patients showed a significant increase in CD40 [66.9 +/-4.8, mean fluorescence intensity (MFI)] and CD40L (14.9 +/-1.8, MFI) co-expression on platelets as well as sCD40L (13.7 +/-1.7 ng/mL) compared with non-restenotic patients and controls during the 6 month follow-up period (P<0.01). Elevated sCD40L and CD40L were significantly correlated with the serum level of CRP after percutaneous transluminal coronary angioplasty and with lumen loss during the 6 month followup period. CONCLUSION: The level of CD40L was associated with late restenosis after PCI indicating that restenosis is an inflammatory disorder.     

Relation between upregulation of CD40 system and complex stenosis morphology in patients with acute coronary syndrome

INTRODUCTION Disruption of vulnerable atheromatous plaque isthe most common pathogenic mechanism in acute coro-nary syndromes (including non Q wave AMI, Q waveAMI and unstable angina). Integrity of the extracellularmatrix constitutes a critical determinant in the stabilityof coronary atheromata. In particular, degradation offibrillar collagen may decrease the ability of the fibrouscap to withstand mechanical stress. Several membersof the MMP family contribute to collagen degrada…     

再生障碍性贫血患者外周血及骨髓sCD40L水平检测及意义

目的：探讨可溶性CD40配体（sCD40L)在再生障碍性贫血（再障）患体内的变化及其发病机制中的作用。方法：用ELISA方法检测40例再障患及正常人外周血及骨髓中sCD40L水平；用免疫荧光标记技术和流式细胞仪分析患骨髓及外周血淋巴细胞的表型。结果：再造患外周血及骨髓sCD40L较正常人均显降低（P均＜0．001）；患可溶性CD40L水平与外周血粒细胞和血小板计数相关；患骨髓及外周血CD4^ 细胞比例下降，CD4／CD8比值降低。结论：sCD40L降低可能是再障发病的重要因素之一，其外周血及骨髓水平的检测对明确诊断和判断预后有重要的临床意义，重组人可溶性CD40L的应用可能为再障的治疗开辟另一新的途径。     

Soluble CD40L and its role in essential hypertension: diagnostic and therapeutic implications

Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage and has been regarded as a molecular link between inflammation, thrombosis and angiogenesis. Given the increasingly recognized theory that hypertension is in part an inflammatory disorder, the contribution of CD40/CD40L dyad is becoming one of the outstanding puzzles in the pathophysiology of hypertension. CD40/CD40L signaling appears, in fact, like a versatile pathway that vehicles information within vascular cells. Several distinct lines of investigation in the context of hypertension dealing with low-grade inflammation are now merging, with CD40/CD40L system as the missing link. As an example, recent data suggest that the vasoactive peptide angiotensin II promotes and augments the inflammatory activation induced by CD40/CD40L ligation in human vascular cells. Accordingly, sCD40L levels are elevated in hypertensive patients and might discriminate hypertensive patients at a high risk of cardiovascular events. This review will summarize the present understanding of the contribution of sCD40L to inflammation, thrombosis and neoangiogenesis in hypertension. Furthermore, given the well established effects that antihypertensive drugs exert on the vasculature beyond blood pressure lowering (pleiotropic effects), we will also discuss the effects of antihypertensive treatment on these phenomena.     

Association between serum levels of soluble CD40/CD40 ligand and organ damage in hypertensive patients

1. CD40 and CD40 ligand (CD40L) have a critical role in the pathophysiology and risk prediction of coronary artery syndrome, including atherothrombosis and atherosclerosis. However, the contribution of the CD40/CD40L dyad, especially the soluble form of CD40L (sCD40L), to the pathophysiology of hypertension and associated organ damage remains unknown. 2. In the present study, serum levels of CD40 and sCD40L were measured in 328 hypertensive patients with varying degrees of organ damage. The data revealed that serum levels of CD40 were significantly greater in patients with severe, but not mild, organ damage compared with patients without any organ damage. There were no significant differences in serum concentrations of sCD40L between patients with no, mild and severe organ damage. Concentrations of soluble CD40 were comparable in patients with mild organ damage that included left ventricular hypertrophy, retinal damage, renal dysfunction and proteinuria. In contrast, concentrations of soluble CD40 were increased significantly in patients with certain forms of severe organ damage, specifically stroke, but not coronary and peripheral artery disease. 3. Collectively, our data indicate that upregulation of the CD40 system in hypertensive patients with certain forms of severe end‐organ damage may contribute to the pro‐inflammatory, pro‐atherogenic and prothrombotic milieu in hypertension.     

Differential downstream effects of CD40 ligation mediated by membrane or soluble CD40L and agonistic Ab: a study on purified human B cells

With the addition of various cytokines, the CD40-CD40 ligand (CD40L) system can act as a T-helper cell surrogate to permit B lymphocytes to produce large amounts of polyclonal Ig. In the present study, we tested six CD40-CD40L stimulation models: (i, ii) soluble agonistic 89 and G28.5 mAbs ; (iii, iv) 89 and G28.5 bound via their Fc fragments on CDw32-transfected mouse fibroblasts; (v) purified, soluble, trimeric human CD40L molecules (sCD40L); and (vi) human CD40L expressed by a CD40L-transfected mouse fibroblastic cell line (LCD40L). Target B cells consisted of purified blood and tonsillar CD19+ lymphocytes cultured in the presence of CD40 stimuli and IL-2 and IL-10, added at the onset of each B cell culture. A) There was differential expression of CD69, CD80 and CD86 exposure to sCD40L and LCD40L was ensued by the strongest % MFI changes over control. B) In blood B cells, mAbs and sCD40L induced IgA, IgM and IgG production almost equally well; LCD40L proved less efficient. In contrast, in tonsil B cells, LCD40L induced significantly more IgA, IgG1, IgG3 and IgM production than other signals. Using certain CD40/CD40L stimuli to model in vitro Ig production, a system used regularly in many laboratories, may affect the interpretation based on the cell type and on the CD40/CD40L system used.     

硫酸氢氯吡格雷对非ST段抬高急性冠脉综合征患者血清hs-CRP及sCD40L的影响

目的 观察硫酸氢氯吡格雷(波立维,Plavix)对非ST段抬高急性冠脉综合征(NSTE-ACS)患者血清高敏C反应蛋白( hs-CRP)及可溶性CD40配体(sCD40L)的影响.方法 将40例NSTE-ACS患者随机分为两组:常规治疗组20例和氢氯吡格雷治疗组20例(在常规治疗基础上加用氢氯吡格雷,首次顿服300 mg,次日起75 mg/d,连服14d).采用酶联免疫吸附法(ELISA)测定全部患者治疗前、后血清hs-CRP及sCD40L浓度.结果两组患者治疗后,血清hs-CRP、sCD40L浓度均较治疗前显著降低(P＜ 0.05 );氢氯吡格雷治疗组治疗前、后血清hs-CRP、sCD40L降低程度较常规治疗组更为显著(P＜0.05).结论 NSTE-ACS患者在常规治疗基础上加用氢氯吡格雷能明显降低血清hs-CRP、sCD40L浓度,有效减轻动脉粥样硬化炎症反应,降低动脉粥样斑块不稳定性.     

血清可溶性CD40L和C反应蛋白在慢性血透患者外周血管钙化的作用

目的 探讨血清可溶性白细胞分化抗原40配体（sCD40L）和C反应蛋白（CRP）在尿毒症血液透析患者外周血管钙化中的作用.方法 尿毒症血液透析患者40例因动静脉内瘘失功行内瘘重建术,术中取桡动脉残端行钙化染色观察血管钙化情况,依据血管钙化有无及程度分组,同时检测血清sCD40L和CRP水平,比较钙化组与非钙化组,不同程度钙化组间血清sCD40L和CRP水平的差异.结果 40例患者桡动脉钙化染色检出血管钙化23例,其中重度钙化9例,轻中度钙化14例,钙化组血清sCD40L和CRP水平高于非钙化组,有统计学差异（P〈0.01）.重度钙化组sCD40L和CRP水平高于轻中度钙化组.有统计学差异（P〈0.05）.血清sCD40L和CRP含量呈正相关.结论 sCD40L和炎症反应可能参与了尿毒症血液透析患者外周血管钙化的发生.     

行PCI术中冠脉内应用替罗非班对急性心肌梗死患者血清hs-CRP和sCD40L的影响

目的 探讨行经皮冠状动脉介入治疗(PCI)术中冠脉内应用替罗非班对急性心肌梗死患者血清超敏C反应蛋白(hs-CRP)和可溶性CD40配体(sCD40L)的影响.方法 行PCI手术的82例急性心肌梗死患者随机分为两组,对照组40例,治疗组42例;对照组采用常规治疗,治疗组在行PCI术中冠脉内注射替罗非班.观察PCI术后的血流,血清hs-CRP和sCD40L.结果 梗死相关冠脉血流(TIMI)达到3级的对照组33例,治疗组40例,两组有统计学差异(P<0.05).两组在治疗后均明显改善了患者血清hs-CRP和sCD40L,并且治疗组改善更加明显(P<0.05),具有统计学意义.结论 PCI术中冠脉内使用替罗非班可以明显改善急性心肌梗死患者的血流,减少血清hs-CRP和sCD40L的表达.