阿托伐他汀钙抑制高糖诱导的人脐静脉内皮细胞内皮微粒释放及细胞凋亡

目的：探讨阿托伐他汀钙对高糖诱导的人脐静脉内皮细胞（HUVEC）内皮微粒释放和细胞凋亡的影响.方法：取生长良好的HUVEC进行实验.将细胞分为3组：对照组（5.5mmol/L葡萄糖）、高糖组（33.3mmol/L葡萄糖）和阿托伐他汀干预组.干预组首先用不同浓度的阿托伐他汀钙（0.01～10μmol/L）分别作用lh,而后加入33.3mmol/L葡萄糖共同孵育24,48,72h.应用MTT比色法检测细胞的生存率.采用流式细胞仪分别检测HUVEC内皮微粒释放以及细胞凋亡率.应用Griess还原法检测培养细胞上清液中一氧化氮（NO）浓度.结果：阿托伐他汀钙减轻高糖对HUVEC的损伤,阿托伐他汀组细胞形态基本完好.阿托伐他汀钙降低高糖诱导的HUVEC内皮微粒释放和细胞凋亡率,且均具有浓度和时间依赖性（P均〈0.05）.阿托伐他汀钙升高高糖诱导的NO含量,使其趋于正常.此作用在0.1～10μmol/L阿托伐他汀钙浓度区间作用24～48h时效果最明显（P均〈0.05）.结论：阿托伐他汀钙抑制高糖诱导的HUVEC内皮微粒释放及细胞凋亡,并通过调节内皮微粒和NO平衡起到保护HUVEC作用.     

红细胞微粒与深静脉血栓形成关系的研究进展

红细胞微粒是在各种刺激因素下由红细胞释放的小囊泡，其产生和释放贯穿于红细胞的整个老化过程。相关研究证明红细胞微粒具有调节血管内皮细胞功能及激活凝血系统的作用，其与心血管疾病的发生、发展有这密切联系，尤其在深静脉血栓形成等血栓性疾病中发挥着重要作用。随着对红细胞微粒研究的不断深入，其可能作为一种深静脉血栓形成诊断外周血生物标志物。现主要对红细胞微粒与深静脉血栓形成的关系研究进行一概述。     

内皮微粒在肾移植急性排斥反应中的诊断作用

背景：血管内皮细胞的变化与移植排斥反应的关系极为密切，内皮微粒脱落于激活或凋亡的内皮细胞，能直接而特异地反映血管内皮细胞的变化，检测血浆中内皮微粒对肾移植排斥反应的诊断监测具有一定的理论和实际意义。 目的：探讨肾移植急性排斥反应时循环内皮微粒的数量和表型的变化及与急性排斥反应之间的关系。 方法：建立同基因和同种异基因大鼠腹腔原位肾移植模型；移植后5 d苏木精-伊红染色观察肾组织的病理学改变，并进行Banff评分；采用免疫组化法检测肾组织中细胞间黏附分子1表达；采用流式细胞术检测血浆中CD144+内皮微粒数量及细胞间黏附分子1+/CD144+内皮微粒的数量；分析内皮微粒的数量和表型与肾组织病理变化的关系。 结果与结论：与同基因移植组比较，异基因移植组Bnaff评分明显增加(P < 0.01)，肾组织中细胞间黏附分子1表达明显增强(P < 0.01)；与同基因移植组比较，异基因移植组CD144+内皮微粒的数量和携带细胞间黏附分子1的内皮微粒的水平明显增加(P < 0.01)。内皮微粒的数量与移植肾急性排斥反应的程度呈正相关(P < 0.01)，携带细胞间黏附分子1内皮微粒的水平与移植肾脏中细胞间黏附分子1的表达呈正相关(P < 0.01)。提示肾移植后对内皮微粒数量和表型进行检测对诊断急性排斥反应的发生有一定意义。     

Platelets microparticles as a link between micro- and macro-angiopathy in young patients with type 1 diabetes

The development of vasculopathies in diabetes involves multifactorial processes. Increased levels of platelets-derived microparticles (PMPs) have been reported in diseases associated with thrombotic risk, but few data are available in diabetes. We explored the level of PMPs in young patients with type 1 diabetes in relation to inflammation, glycemic control, micro-vascular complications and carotid intima media thickness (CIMT). Eighty children and adolescents with type 1 diabetes were divided into two groups according to the presence of micro-vascular complications and compared with 40 healthy controls. Patients were subjected to medical history, clinical examination and assessment of high-sensitivity C-reactive protein (hs-CRP), HbA1c, urinary albumin creatinine ratio (UACR), flow cytometric analysis for PMPs using anti-CD41b and CIMT. PMP levels were significantly increased in all patients with type 1 diabetes (2.92?±?1.3%) whether with micro-vascular complications (3.46?±?1.11%) or those without complications (2.37?±?1.28%) compared with healthy controls (1.28?±?0.64%; p?<?0.001). CIMT was significantly elevated in all patients, and the highest levels were among those with micro-vascular complications (p?<?0.001). Significant positive correlations were found between PMPs and body mass index, HbA1c, serum creatinine, total cholesterol, UACR, hs-CRP and CIMT (p?<?0.05). Multiple linear regression analysis showed that HbA1c, UACR, hs-CRP and CIMT were independently related to PMPs levels in type 1 diabetes. According to Receiver operating characteristic curve analysis, the cutoff value of PMPs at 2.48% could differentiate patients with and without micro-vascular complications with a sensitivity of 80% and specificity of 73.3%. PMPs are elevated in patients with type 1 diabetes and can be considered as an early marker of micro-vascular complications and subclinical atherosclerosis.     

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.