瑞舒伐他汀对急性心肌梗死患者树突状细胞功能的影响

目的探讨瑞舒伐他汀对急性心肌梗死患者（AMI）树突状细胞（DC）功能的影响。方法将45例AMI患者分为常规治疗组（22例）和常规治疗加瑞舒伐他汀组（23例）,分别于治疗前及治疗后2周抽血,分离外周血单个核细胞,制备DC。检测DC表型（CD86）、DC对同种异体T淋巴细胞的刺激能力、DC吞噬功能和凋亡细胞数、MLR上清液中的细胞因子,并与对照组比较。结果与对照组比较,AMI患者DC表面CD86的表达明显增高,对T淋巴细胞刺激能力增强,经DC刺激的淋巴细胞分泌致炎症细胞因子（IL-6,IL-12,肿瘤坏死因子a）增多,抑制炎症细胞因子（IL-10）减少,差异均有统计学意义（P〈0．01）。用瑞舒伐他汀前CD86的表达与血低密度脂蛋白胆固醇（LDL-C）水平正相关（r=0．63,P〈0．01）;瑞舒伐他汀抑制DC功能的同时显著降低血hs-CRP水平;且CD86与hs—CRP水平正相关（r=O．59,P〈0．01）。结论急性心肌梗死患者DC功能亢进,瑞舒伐他汀抑制斑块炎症的机制之一可能是抑制DC的功能。     

树突状细胞及其免疫调节功能

树突状细胞（DC）首先由Stemman于1973年从小鼠淋巴结中分离成功,因状似树突而得名,细胞表面突起有利于其与周围细胞广泛接触。近年研究显示,DC起源于骨髓CD去造血干细胞,具有异质性,能识别内外抗原、调节免疫功能,在机体免疫系统中处于中心地位,可保持免疫激活与免疫耐受之间的平衡。现将其免疫调节功能综述如下。     

季节对急性心肌梗死发病的影响

目的探讨季节对急性心肌梗死(AMI)发病的影响。方法选取2016年7月至2019年12月入住东莞市人民医院与哈尔滨医科大学附属第二医院心内科的2610例冠心病患者,收集基础资料。依据国际通行的季节划分标准,按发病时间将患者分组:春季组(3~5月),夏季组(6~8月),秋季组(9~11月),冬季组(12~2月)。结果基础资料显示4组患者高血压、糖尿病、低密底脂蛋白胆固醇(LDL-C)、性别的分布差异无统计学意义。春季组与冬季组的患者年龄稍大,而秋季组和冬季组的患者吸烟比例较高。各组男性AMI患者的发病比例均高于女性(P=0.001)。Logistic回归分析显示,以春季组作为参照,秋季组和冬季组与AMI的发病独立相关(OR=2.274,95%CI 1.487~3.478,OR=1.512,95%CI 1.023~2.235),男性(OR=2.424,95%CI 1.733~3.391)、吸烟(OR=1.862,95%CI 1.332~2.603)和低密度脂蛋白胆固醇(LDL-C)(OR=2.797,95%CI 2.356~3.320)是AMI发病的独立危险因素。ROC分析提示,秋、冬季诊断AMI的AUC值为0.540,95%CI 0.503~0.578,P=0.033。结论秋、冬季是AMI发病的独立因素。     

急性心肌梗死发病时间和节气规律的研究

目的 了解急性心肌梗死(AMI)患者的发病时间、季节及二十四节气的规律,以指导AMI的防治.方法 将2009年9月-2011年9月收住我院ICU的AMI患者315例,根据胸痛开始出现的时间进行分析,分别根据发病的时间点、发病的季节、发病的节气分布进行分析.结果 315例AMI患者,按照时间点分析发病时间点高峰在07:00～12:00,其次是00:01～06:00;按照春季(1月～3月)、夏季(4月～6月)、秋季(7月～9月)和冬季(10月～12月)将一年分成4个季节进行分析,发病季节高峰在春季;按照二十四节气进行分析,发病节气高峰在清明和处暑.结论 AMI的发病的时间段、季节以及二十四节气分布均具有相应的高峰.     

树突状细胞与支气管哮喘研究进展

树突状细胞（dendriti ccells,DC）通过激活初始T细胞、诱导Th2免疫应答偏移和维持气道炎,以及负性调节作用,影响支气管哮喘（简称哮喘）疾病的发生、发展,是哮喘免疫应答的启动者、参与者和节者。DC在免疫应答中的关键地位提示我们它可作为防治哮喘疾病的一个重要靶点。     

树突状细胞与支气管哮喘研究进展

树突状细胞(dendritic cells,DC)通过激活初始T细胞、诱导Th2免疫应答偏移和维持气道炎症,以及负性调节作用,影响支气管哮喘(哮喘)疾病的发生、发展,是哮喘免疫应答的启动者、参与者和调节者.DC在免疫应答中的关键地位提示我们它可作为防治哮喘疾病的一个重要靶点.     

脑卒中的发病季节和时间规律分析

目的用圆分布法分析南昌市气象条件下脑卒中的发病时间特点与季节规律。方法收集南昌市大型综合性三级甲等医院2003～2008年因脑卒中就诊的住院病例资料,分析脑卒中的发病时间特点,用圆分布分析其发病集中趋势。结果 (1)脑出血、脑梗死患者平均年龄为(60.54±13.67)岁和(65.79±12.35)岁,男女性别比分别为1.78∶1和1.62∶1。(2)脑出血发病有明显的季节性,冬季好发,夏季低发;脑梗死发病无明显季节性。(3)脑出血2003～2008年发病均有明显的集中趋势(均P<0.05),六年合计发病也有一个集中趋势,平均角是11.236 524度(P<0.05),相当于1月12日;脑梗死只有2003年和2005年的平均角有意义(P<0.05),六年合计的平均角无统计学意义(P>0.05)。结论南昌市脑出血与脑梗死的好发年龄分别为(60.54±13.67)岁和(65.79±12.35)岁,男性较女性多发。脑出血发病有明确的季节性,冬季好发,年度发病集中于冬季的3个月份(11月至次年1月);脑梗死的季节性不明显。     

慢性乙型肝炎树突状细胞表型和功能的变化与免疫耐受

目的 观察慢性乙型肝炎病毒（HBV）感染者树突状细胞（DC）形态和功能的改变。方法 从13例慢性乙型肝炎患者和11例健康人外周血中分离和培养DC,观察DC的形态,用流式细胞仪检测DC表面标记HLA－DR、CD1a、CD80和CD86的表达,用^3H-TdR掺入法测定DC诱导混合性淋巴细胞反应（MLR）的能力。结果 正常DC较慢性乙型肝炎患者在形态上更为典型,不规则,HLA－DR、CD80和CD86分子的表达水平较高（P＜0.05）,诱导MLR的能力较强（P＜0.05）。结论 慢性乙型肝炎患者外周血DC处于不完全成熟状态,其免疫刺激能力较低。     

Ghrelin增强树突状细胞的免疫功能

目的 探讨Ghrelin能否调节树突状细胞(DC)的免疫功能.方法 自人外周血单核细胞制备DC;以TNF-α诱导DC成熟,然后以Ghrelin刺激DC;检测经Ghrelin刺激后DC表面B7-H1的表达和细胞因子的表达,并进一步检测该DC诱导T淋巴细胞增值能力.结果 Ghrelin下调TNF-a诱导的B7H1的表达,并进一步增强其诱导T淋巴细胞增殖活性;抗B7-H1抗体能增强该DC诱导T淋巴细胞增值活性;特异性的PKC抑制剂能逆转Ghrelin对DC免疫功能的调节.结论 Ghrelin通过抑制B7-H1表达增强DC的免疫功能,提示Ghrelin将可能在肿瘤和感染性疾病中发挥重要作用.     

树突状细胞与肺部病关系研究现状

树突状细胞（DC）是功能最强的抗原呈递细胞（APC）。与其他APC如巨噬细胞、B细胞相比,DC具有独特的刺激处女（naive)型T细胞的能力。DC在启动免疫方面及决定免疫走向方面起着关键作用。肺部DC主要存在于气道和靠近肺泡的间质中。许多肺部疾病与DC有关。本文综述DC在肺部的分布,DC的成熟和功能,DC与T、B淋巴细胞,以及DC与呼喘、肺部肿瘤、支气管扩张等部疾病的关系,其中重点综述DC和喘的关系。     

IL-6 levels in acute and post myocardial infarction: their relation to CRP levels, infarction size, left ventricular systolic function, and heart failure

BACKGROUND: Inflammatory mechanisms in heart disease are of great interest. The proinflammatory cytokine interleukin (IL) 6 has been linked to increased morbidity in unstable angina pectoris and depressed myocardial function in heart failure (HF). METHODS: We studied the relation of IL-6 levels to C-reactive protein (CRP), infarction size, left ventricular function, and HF in acute myocardial infarction (MI) and after hospital discharge in 31 consecutive patients (19 males, mean age 69+/-13 years). Blood sampling for IL-6 was performed on admittance, four times on day 1, twice on day 2, and once daily on days 3-5, and 6 and 12 weeks later. Clinical signs of HF were evaluated daily during hospitalization and after 6 and 12 weeks. Echocardiography was performed on day 3 and at 6 weeks. RESULTS: IL-6 showed a curved time course with elevated levels already on admittance (mean+/-S.D. 19.3+/-26.9 ng/l), thereafter increasing to a peak on days 1 and 2 (maximum 68.5+/-152.9 ng/l), and then declining rapidly to lower, although not normalized, levels during hospitalization and at 6 and 12 weeks. CRP showed a similar time pattern, but with a later peak and a seemingly less rapid decline in levels. Mean levels of IL-6 and CRP on days 1-5 correlated highly (r=0.794, p<0.0001). IL-6 and infarction size did not correlate. HF during hospitalization and at 6 weeks was not related to IL-6; however, patients with HF at 12 weeks had higher IL-6 levels, both at 6 and 12 weeks. Patients on ACE inhibitors or diuretics at discharge had higher IL-6 levels at 6 weeks. IL-6 during hospitalization was not related to LVF; yet, patients with depressed LVF in the hospital and at 6 weeks had higher IL-6 levels at 6 and 12 weeks. CONCLUSIONS: IL-6 in acute MI shows a curved time course and is highly correlated to CRP. It peaks on days 1 and 2 and remains elevated even after 12 weeks. Increased IL-6 levels after hospital discharge are associated with HF and depressed LVF. Whether anti-inflammatory agents will influence left ventricular dysfunction and outcome postacute MI has yet to be determined.     

急性心肌梗塞患者口服氯吡格雷后白细胞减少与季节的关系

目的：探讨急性心肌梗死患者口服氯吡格雷后白细胞减少与季节的关系。方法：对317例急性心肌梗死患者按季度进行分组,比较组间口服氯吡格雷后白细胞水平的变化。结果：白细胞减少发生率在冬季（16．83％）明显高于春季（7．04％）、夏季（7．23％）、秋季（9．68％）,P〈0．05。结论：口服氯吡格雷后白细胞减少与季节相关,冬季最易出现。     

The novel role of mast cells in the microenvironment of acute myocardial infarction

Mast cells are multifunctional cells containing various mediators, such as cytokines, tryptase, and histamine, and they have been identified in infarct myocardium. Here, we elucidated the roles of mast cells in a myocardial infarction (MI) rat model. We studied the physiological and functional roles of mast cell granules (MCGs), isolated from rat peritoneal fluid, on endothelial cells, neonatal cardiomyocytes, and infarct heart (1-hour occlusion of left coronary artery followed by reperfusion). The number of mast cells had two peak time points of appearance in the infarct region at 1 day and 21 days after MI induction in rats (p < 0.05 in each compared with sham-operated heart). Simultaneous injection of an optimal dose of MCGs modulated the microenvironment and resulted in the increased infiltration of macrophages and decreased apoptosis of cardiomyocytes without change in the mast cell number in infarct myocardium. Moreover, MCG injection attenuated the progression of MI through angiogenesis and preserved left ventricular function after MI. MCG-treated cardiomyocytes were more resistant to hypoxic injury through phosphorylation of Akt, and MCG-treated endothelial cells showed enhanced migration and tube formation. We have shown that MCGs have novel cardioprotective roles in MI via the prolonged survival of cardiomyocytes and the induction of angiogenesis.     

急性心肌梗死患者血管内皮细胞损伤的研究

目的 :研究急性心机梗死 (AMI)患者血管内皮细胞的损伤和功能变化。方法 :6 0例 AMI患者为试验组 ,6 0例健康人作为对照组。以循环内皮细胞 (CEC)作为血管内皮损伤的指示物 ,血浆内皮素 (ET- 1)反映血管内皮的功能变化。动态测定患者在入院后 72 h内的血浆 ET- 1水平 ,CEC计数和左室射血分数 (L VEF)值 ,对照组同时测定。结果 :试验组患者血浆 ET- 1和 CEC均在 AMI早期 4h就达峰值 ,随后逐渐下降 ,但在 72 h内各测定值都高于正常对照组 (P<0 .0 1) ,试验组患者的 ET- 1和 CEC呈显著的正相关 (P<0 .0 0 1)。结论 :血浆 ET- 1和 CEC水平在 AMI早期显著增加 ,可作为心肌梗死内皮细胞损伤和功能变化的指标。     

冠状动脉内自体骨髓单个核细胞移植治疗急性心肌梗死患者的疗效

目的:探讨急性心肌梗死患者自体骨髓单个核细胞经冠状动脉移植的安全性和对心功能的保护作用。方法:2003年3月以来,84例急性心肌梗死患者急诊静脉溶栓或急诊经皮冠状动脉成形术(PTCA)加支架治疗后2周内行择期冠状动脉造影或PTCA加支架治疗,其中50例抽取骨髓40ml,提取单个核细胞,经冠状动脉注入,另34例不做自体骨髓单个核细胞经冠状动脉移植,作为对照组。81例患者术前和术后6个月、2年均行多巴酚丁胺负荷试验(另3例未完成超声心动图随访观察)。结果:治疗组患者临床随访无明显不良反应,心功能明显改善,运动耐量增加。多巴酚丁胺负荷试验左室射血分数(LVEF)和室壁运动记分指数(WMSI)显著改善,峰值LVEF和WMSI与基础状态LVEF和WMSI的差值在治疗前后相比,与对照组相比均差异有统计学意义。结论:自体骨髓单个核细胞经冠状动脉移植治疗急性心肌梗死患者,经6个月～2年的临床观察无明显不良反应,具备安全性,多巴酚丁胺负荷试验显示出自体骨髓单个核细胞治疗对梗死后心功能有保护作用。     

Enhanced functional response of CD133+ circulating progenitor cells in patients early after acute myocardial infarction

Aims: Circulating progenitor cells (PC) may contribute to myocardialrecovery following infarction. Growth factors including VEGFare produced during ischaemia and stimulate PC release and activation.In this study, we focused on the functional chemotactic responseof PC to VEGF in subjects early after myocardial ischaemia. Methods and results: Number and phenotype of PC were characterized using flow-cytometry.CD133⁺PC were isolated from peripheral blood using positiveMACS isolation. The chemotactic response towards members ofthe VEGF family (VEGF-A, PlGF-1, and VEGF-E) was analysed inthree groups: (i) early period following acute myocardial infarction(days 2–4) treated with primary PCI (AMI) (n = 35), (ii)stable coronary artery disease (CAD) (n = 35), and (iii) controls(CTR) (n = 20). CD133⁺PC number was 2-fold higher in AMI whencompared with CAD and CTR (P = 0.0001), whereas CAD was notdifferent from CTR. The chemotactic response of CD133⁺PC toVEGF-A, PlGF-1, and VEGF-E was significantly enhanced (2-fold)in AMI when compared with CAD (P = 0.0001). While the increaseof the VEGFR-1-mediated/PlGF-triggered response was rapid (2days following infarction), the VEGFR-2-mediated/VEGF-E-triggeredresponse was maximally increased on day 4 post-AMI, thus correlatingwith the kinetics of maximal inflammatory activation reflectedby increased CRP levels (P = 0.019). Conclusion: The enhanced chemotactic response of CD133⁺PC following myocardialinfarction represents a novel principle potentially involvedin cardiovascular repair early after myocardial infarction.Acute inflammatory processes are closely associated with thisincreased cellular function.     

Significance of total and differential leucocyte count in patients with acute myocardial infarction treated with primary coronary angioplasty.

AIMS: The aim of this study was to correlate total and differential leucocyte (WBC) count with myocardial blush, peak CK levels, and left ventricular (LV) functional recovery at 6 months in 238 consecutive acute myocardial infarction (MI) patients treated with successful primary coronary angioplasty (PCI). METHODS AND RESULTS: Total and differential WBC counts were measured on admission and every 24 h for at least 4 days after PCI. ST-segment resolution and myocardial blush were evaluated immediately after successful primary PCI. LV functional recovery (defined as improvement involving at least two segments, or at least one segment, when only two were asynergic on the basal examination) was obtained through echocardiographic evaluation of LV wall motion at the baseline and at 6 months. Basal CK (P<0.001) and increased neutrophil levels (P<0.001) were the only independent factors related to peak CK, whereas neutrophils and monocytes peaks were related to ST-segment resolution as well as to myocardial blush grade (MBG) 2-3. MBG 2-3 and monocytes number (both as continuous values as well as percentile values) were the only variables independently associated with 6-month LV functional recovery. CONCLUSION: The present study shows that neutrophils and monocytes counts on the first days after acute MI treated with primary PCI are related to markers of effective myocardial reperfusion such as MBG 2-3 and ST-segment resolution. However, only monocytes and MBG are significantly and independently associated with contractile recovery of the infarcted area at 6 months.     

Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction

Background

Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function.

Methods

Sixty-two patients with acute MI treated by percutaneous coronary intervention, with depressed LV ejection fraction (LVEF) were randomized in a double-blinded fashion to IVIg as induction therapy and thereafter as monthly infusions or placebo for 26 weeks. The primary end point was changes in LVEF from baseline to 6 months as assessed by MRI.

Results

Our main findings were: (i) LVEF increased significantly from 38 ± 10 (mean ± SD) to 45 ± 13% after IVIg and from 42 ± 9 to 49 ± 12% after placebo with no difference between the groups. (ii) The scar area decreased significantly by 3% and 5% in the IVIg and placebo group, respectively, with no difference between the groups. (iii) During the induction therapy (baseline to day 5), IVIg induced both inflammatory (e.g., increase in tumor necrosis factor α and monocyte chemoattractant protein-1) and anti-inflammatory (e.g., increase in interleukin-10 and decrease in leukocyte counts) variables, but during maintenance therapy there were no differences in changes of inflammatory mediators between IVIg and placebo.

Conclusions

IVIg therapy after ST elevation MI managed by primary PCI does not affect LV remodeling or function. This illustrates the challenges of therapeutic intervention directed against the cytokine network, to prevent post-MI remodeling.     

Central haemodynamics in acute myocardial infarction in relation to mortality and peak enzyme activity

The relation of central haemodynamic changes to subsequent mortalityand peak enzyme activity was investigated in 190 patients withacute myocardial infarction. The mean delay time from onsetof symptoms to the haemodynamic study was 7.2 hours. Major exclusioncriteria were heart rate < 65beats min^–1, systolicblood pressure < 105 mmHg and lung rales to a distance of> 10 cm above the lung bases. Nine patients (4.7%) died within15 days and 16 patients (8.4%) within 90 days after the infarction.Compared to survivors, non-survivors were characterized by baselinedepression of cardiac index, stroke volume index and left ventricularstroke work index, while pulmonary capillary wedge pressureand peripheral resistance were increased. However, a wide overlapbetween survivors and non-survivors makes the predictive valuelow in the individual patient. Peak serum aspartate aminotransferase (S-ASAT) activity wasweakly related to baseline pulmonary capillary wedge pressure(r = 0.28; P< 0.001) and stroke volume index (r = –0.22;P7lt;0.01). The correlation to pulmonary capillary wedge pressurewas only found in anterior (r = 0.34) infarcts. Peak serum lactatedehydrogenase (LD¹) was not correlated with baseline haemodynamics.