联合检测冠心病患者ⅡA分泌型磷脂酶A2和脂蛋白相关磷脂酶A2的临床意义

目的 探讨冠心病患者联合检测血清ⅡA分泌型磷脂酶A2 （secretory groupⅡA phospholipase A2,ⅡA-sPLA2）及脂蛋白相关磷脂酶A2 （LP-PLA2）对于其诊疗的意义.方法 对健康对照组50例、急性心肌梗死（AMI）组13例、稳定型心绞痛（UAP）组17例和不稳定型心绞痛（SAP）组70例的生化指标（主要ⅡA-sPLA2和LP-PLA2水平）进行测定,统计分析各组之间的差异是否有统计学意义.结果 随着冠心病患者病变程度加剧,HDL水平有降低的趋势,即AMI组比SAP和UAP组患者的HDL水平均高,三组相比差异均有统计学意义（t=3.013-3.987,均P＞0.05）.ⅡA-sPLA2和LP-PLA2在冠心病各亚型患者中的水平明显比对照组高,且AMI组比SAP和UAP组,SAP比UAP患者的水平均高,差异有统计学意义（t=3.507-9.967,均P＜0.05）.ⅡA-sPLA2和LP-PLA2指标之间呈正相关关系（r=0.657,P＜0.05）,HDL分别和ⅡA-sPLA2与LP-PLA2之间呈显著的负相关关系（r=-0.351,-0.294,均P＜0.05）.结论 ⅡA-sPLA2与LP-PLA2含量将可能是治疗冠状动脉粥样硬化和预防心血管疾病的新指标.     

脂蛋白相关性磷脂酶A2的活性与冠心病风险预测的相关性研究

目的观察血清中脂蛋白相关磷脂酶A2酶活性(Lp-PLA2)与冠心病(CHD)的相关性,探讨Lp-PLA2是否是冠心病的危险因子。方法分别对239例经降脂治疗的冠心病患者(CHD1组)、154例未经降脂治疗的冠心病患者(CHD2组)和378例健康对照者(NC组)的各种生化指标以及临床基本资料进行检测和调查。应用免疫比浊法(美国Cayman公司提供PAF-AH活性测定试剂盒),测定Lp-PLA2的酶活性。结果未经降脂治疗的冠心病组和经降脂治疗的冠心病组的Lp-PLA2活性明显高于对照组,差异有统计学意义[35.01(15.96,53.32)nmol/ml/min,28.74(16.72,53.58)nmol/ml/min,22.67(15.55,28.62)nmol/ml/min,P<0.001];校正传统冠心病危险因子(CHO,TG,Hs-CRP,Lp(a),GLU)后,Lp-PLA2活性的最高四分位数与最低四分位数相比,CHD的OR值为3.15(95%CI:1.05-9.50)。结论 Lp-PLA2的活性在冠心病患者中显著升高,是冠心病的危险因子。     

脂蛋白相关磷脂酶A2在冠心病风险评估中的价值

与低密度脂蛋白 (LDL)密切相关的脂蛋白相关磷脂酶A2 (LP PLA2 )能水解致炎因子如血小板活化因子 (PAF)及结构相关的氧化磷脂 ,产生溶血卵磷脂 (Lyso PC)及游离脂肪酸 ,促进动脉粥样硬化的形成 ,在冠心病的发病风险及预防性治疗上 ,LP PLA2 是一个新的有待研究的因子。     

血浆脂蛋白相关性磷脂酶A2、脂蛋白(a)在动脉粥样硬化性脑梗死中的变化及意义

目的 分析动脉粥样硬化性脑梗死(ACI)与血浆脂蛋白相关性磷脂酶A2(Lp-PLA2)、脂蛋白(a)[Lp(a)]水平的关系。方法 采用彩色多普勒超声检查60例ACI患者颈部血管,评估颈部斑块稳定性;同时应用双抗体夹心酶联免疫吸附法(ELISA)检测脑梗死患者和健康体检患者的血浆Lp-PLA2、Lp(a)水平;使用美国国立卫生研究院卒中量表(NIHSS)进行神经功能缺损程度评估。结果 60例ACI患者中易损斑块44例,稳定斑块16例;ACI患者的血浆Lp-PLA2、Lp(a)均显著高于正常对照组(P<0.05);易损斑块组的Lp-PLA2、Lp(a)明显高于稳定斑块组(P<0.05);神经功能缺损程度与血浆Lp-PLA2水平无显著相关性(P>0.05)。结论 Lp-PLA2、Lp(a)升高与动脉粥样硬化性脑梗死密切相关,临床上可通过测定Lp-PLA2、Lp(a)水平来预测脑梗死的发病风险,对预防及有效减少脑梗死复发具有重要意义。     

脂蛋白相关磷脂酶A2与急性动脉硬化性脑梗死的相关性研究

目的研究血清脂蛋白相关磷脂酶A2(Lp-PLA2)水平与急性动脉硬化性脑梗死的相关性,为临床诊断及干预治疗提供依据。方法急性脑梗死组91例、对照组51例。研究Lp-PLA2与颈动脉斑块形成及稳定性、急性脑梗死发生、进展与复发、神经功能缺损程度等之间的关系。统计学处理采用SPSS 19.0分析软件进行分析。结果高血清Lp-PLA2水平是急性动脉硬化性脑梗死的独立危险因素。血清Lp-PLA2水平病例组和对照组两组有斑块者的均高于无斑块者(P0.05),病例组中不稳定斑块组高于稳定组(P=0.004)。血清Lp-PLA2水平复发脑梗死患者明显高于初发脑梗死患者(P0.05)。血清Lp-PLA2水平与神经功能缺损程度呈正相关(r=0.300,P0.01)。结论高血清LpPLA2水平是动脉硬化性脑梗死的独立危险因素。血清Lp-PLA2水平升高与颈动脉粥样硬化斑块的形成及不稳定性有关。复发脑梗死组血清Lp-PLA2水平明显高于对照组。Lp-PLA2水平与神经功能缺损程度呈正相关。     

脂蛋白相关性磷脂酶A2：一种新型的、具有前景的评估心血管危险的生化标记物

动脉粥样硬化及其相关的心血管疾病的发病率和死亡率至今仍居全球首位。尽管加强了干预措施,但心血管残余风险仍相当高。脂蛋白相关性磷脂酶A2（Lp-PLA2）是一种新型的、独立的血管炎症特异性和动脉粥样硬化特异性生化标记物。大量科学和临床研究证实,Lp-PLA2具有促动脉粥样硬化作用,并与心血管事件的发生呈正相关。目前,根据成年治疗小组Ⅲ（ATP Ⅲ）指南,推荐Lp-PLA2作为传统危险因子的辅助指标,从而可以优化对未来心血管风险的评估。令人鼓舞的是,一种口服的Lp-PLA2特异性抑制剂（Darapladib）,其基础研究和临床前期试验取得了显著的成果。同时,有两项正在进行的针对Darapladib的III期临床试验,以评估其改善心血管结局的疗效和安全性。此外,对于中高危的人群,Lp-PLA2对指导危险分层、建立治疗方案和预后评估具有潜在的价值。该文将对Lp-PLA2的生化特性、在动脉粥样硬化中的作用及其在科学和临床研究的结果作出归纳总结。     

脂蛋白相关磷脂酶A2及其与冠心病相关性的研究进展

冠心病是动脉粥样硬化（atherosclerosis,AS）导致器官病变最常见疾病。As是一种炎性疾病,炎症反应参与了As发生的各个环节。在动脉粥样斑块形成的起始、发展以及稳定性丧失和斑块破裂脱落中均起着重要作用。近期的研究表明,     

连续荧光置换法测定磷脂酶A2的方法研究

磷脂酶A2（PLA2）是一种能催化磷脂甘油分子二位（Sn-2）酰基水解的酶，是控制二十烷碳酸生物活性因子合成及血小板活化因子产生的调节酶[1，2]．PLA2是细胞对炎症产生反应和维持内环境平衡的重要酶之一，由于它在炎症早期递质释放中的限速作用成为治疗全身性炎症反应和细胞损伤的一个重要目标[3]．PLA2的活性测定对了解病理进程，合理使用PLA2抑制剂等都有十分重要的意义．传统的PLA2测定方法是滴定法，其特异性和敏感性均不高，已逐渐被淘汰[4]．目前国外有分光光度法[3]，荧光标记底物法[6]，放射性核素标记底物法[7]以及免疫分析…     

血清脂蛋白a、同型半胱氨酸、脂蛋白相关磷脂酶A2联合检测对冠心病患者的应用分析

目的:探析在冠心病患者中检测血清脂蛋白a、同型半胱氨酸、脂蛋白相关磷脂酶A2的临床意义。方法:根据疾病类型选取2018年1月到2018年12月的60例住院的冠心病患者进行分组,主要涉及到三种类型,一是急性心肌梗,二是不稳定型心绞痛,三是稳定型心绞痛,每组各20例患者,并分别纳入研究一组、研究二组、研究三组,另外择取同期60名健康体检者,将其纳入对照组,对不同类型冠心病患者以及健康体检者的血清脂蛋白a、同型半胱氨酸、脂蛋白相关磷脂酶A2进行检测,对照分析检测结果。结果:从性别、年龄、身高、体重、白细胞计数、总胆固醇水平、体质量指数、高血压病史、糖尿病病史、高血脂病史、吸烟史上对比组间均无统计学差异,P>0.05;相比于对照组,研究组患者甘油三酯水平以及低密度脂蛋白胆固醇水平更高,高密度脂蛋白胆固醇更低,P<0.05;经过检测,研究组患者血清脂蛋白a、同型半胱氨酸、脂蛋白相关磷脂酶A2水平均比对照组高,P<0.05。结论:在冠心病患者检测中,血清脂蛋白a、同型半胱氨酸、脂蛋白相关磷脂酶A2三项指标联合应用可以取得显著临床价值,可以作为临床诊疗的重要指标,临床意义显著。     

脂蛋白相关磷脂酶A2与急性缺血性脑卒中的相关性研究

目的 通过检测急性缺血性脑卒中患者血浆脂蛋白相关磷脂酶A2(Lp-PLA2)浓度,探讨两者的关系,为临床诊断、治疗提供依据.方法 选择急性缺血性脑卒中患者(151例)为研究对象,未卒中患者(100例)作对照,血浆Lp-PLA2检测采用酶联免疫吸附法(ELISA).结果 (1)急性缺血性脑卒中组血浆Lp-PLA2浓度高于对照组,差异有统计学意义(t=21.307,P=0.000).血浆Lp-PLA2浓度与急性缺血性脑卒中的风险呈正相关.(2)各型急性缺血性脑卒中血浆Lp-PLA2浓度差异均无统计学意义(P＞0.05).结论 Lp-PLA2是急性缺血性脑卒中的危险标志物,测定Lp-PLA2浓度有助于制定预防策略,为急性缺血性脑卒中的预防及临床治疗提供依据.     

代谢综合征患者脂蛋白相关磷脂酶A2活性变化的特征

目的:脂蛋白相关磷脂酶A2是一项新的与低水平炎症反应有关的炎性标志物,该研究通过检测代谢综合征患者中该酶水平的变化,探讨代谢综合征的炎症反应机制。方法:采用病例-对照研究,健康对照组与代谢综合征组各65例,均为男性。测定两组人群血浆中脂蛋白相关磷脂酶A2活性。结果:与健康对照组相比,代谢综合征患者血浆中脂蛋白相关磷脂酶A2活性较高(76.98比60.58μmol/L.min,P<0.001)。结论:脂蛋白相关磷脂酶A2活性在代谢综合征患者中升高,表现出低水平的炎症反应。     

Diurnal variation in lipoprotein-associated phospholipase A(2) (Lp-PLA(2))

ObjectivesThe aim of our study was to determine the diurnal variation of lipoprotein-associated phospholipase A₂ (Lp-PLA₂), an arterial-specific inflammatory enzyme implicated in the formation of vulnerable, rupture-prone plaque that can identify individuals at high risk for cardiovascular disease. Presently, the diurnal variation of Lp-PLA₂ is not known.Design and MethodsTen men and 8 women (age range: 22–76 years) had a blood sample taken every 4 h over a 24-hour time period. Samples were analyzed for both Lp-PLA₂ mass and activity.ResultsThe mean coefficient of variation (CV) for Lp-PLA₂ mass was 5.9% (ranges from 2.5 to 9.4%) for the 18 subjects. Similarly, the mean CV for Lp-PLA₂ activity was 3.7% (ranges from 1.2 to 6.8%). There were no significant correlations between CV and any of the subject characteristics.ConclusionsThe diurnal variation of Lp-PLA₂ mass and activity is similar to that of well accepted lipoprotein risk factors. With the relatively low diurnal variability, there does not appear to be a need to make sure serial measurements of Lp-PLA₂ mass and activity are taken at the same time of the day.     

不同剂量阿托伐他汀对ACS患者脂蛋白相关性磷脂酶A2的影响

【目的】观察不同剂量阿托伐他汀对急性冠脉综合征（ACS）患者血浆脂蛋白相关性磷脂酶A2（Lp—PLA2）水平的影响。【方法】将46例ACS患者随机分为常规剂量组（常规治疗加阿托伐他汀20mg／d,23例）和强化治疗组（常规治疗加阿托伐他汀40mg／d,23例）,治疗前及治疗10d后清晨空腹采血,以酶联免疫吸附法测定血浆中Lp—PLA2水平,并检测血脂各项指标;同时选用23例健康体检者作为正常对照。【结果】①ACS患者血浆LpPLA2水平明显高于正常对照组（P〈0．001）;②20mg／d和40mg／d阿托伐他汀治疗10d后Lp-PLA2水平较治疗前均有显著下降（P〈0．01）,而强化治疗组下降更为明显（P〈0．01）;③spearman等级相关分析显示,ACS患者血浆Lp-PLA2水平与总胆固醇（TC）及低密度脂蛋白胆固醇（LDL—C）相关,与甘油三酯（TG）和高密度脂蛋白胆固醇（HDL—C）不相关。【结论】ACS患者血浆Lp—PLA2水平增高,短期阿托伐他汀治疗能降低ACS患者Lp-PLA2水平,且呈剂量依赖性。     

25-羟维生素D、脂蛋白相关磷脂酶A2与糖尿病视网膜病变的相关性:单中心回顾性研究

  目的  探讨25-羟维生素D[25-hydroxy vitamin D, 25(OH)D]、脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2, LP-PLA2)与糖尿病视网膜病变(diabetic retinopathy, DR)的相关性。  方法  回顾性收集并分析2014年5月至2017年1月沧州市中心医院内分泌科收治的2型糖尿病患者的临床资料,根据眼底摄片结果,分为糖尿病不伴视网膜病变组(no DR, NDR)组,背景期糖尿病伴视网膜病变(background DR, BDR)组和增殖期糖尿病伴视网膜病变(proliferative DR, PDR)组,选取同期于本院进行体检的健康人作为对照组。比较4组相关生化指标水平,采用Pearson相关分析及多元Logistic回归分析DR的相关及独立危险因素。  结果  共340例符合纳入和排除标准的2型糖尿病患者入选本研究,其中NDR组125例、BDR组118例、PDR组97例, 对照组100例。4组间的性别、年龄、体质量指数、收缩压、舒张压、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、空腹血糖差异无统计学意义(P均＞0.05);NDR组、BDR组、PDR组的病程逐渐增长(P=0.003),NDR组、BDR组、PDR组糖化血红蛋白A1C(glycated hemoglobin A1c, HbA1c)、糖化白蛋白(glycated albumin, GA)、血清胱抑素C(serum cystatin C, Cys-C)、LP-PLA2均显著高于健康对照组, 25(OH)D显著低于健康对照组(P均＜0.05);NDR、BDR、PDR组间两两比较,HbA1c、GA、Cys-C、LP-PLA2、25(OH)D差异亦有统计学意义(P均＜0.05)。Pearson相关分析显示,病程、HbA1c、GA、Cys-C及LP-PLA2与DR呈正相关(P均=0.000),25(OH)D与DR呈负相关(P=0.000)。多元Logistic回归分析显示,病程、HbA1c、Cys-C、LP-PLA2、25(OH)D与DR及其严重程度均独立相关(P均＜0.05)。  结论  25(OH)D 、LP-PLA2水平与DR的发生、发展密切相关,25(OH)D是其保护因素,而LP-PLA2是其危险因素。     

Phospholipase A(2)s in cell injury and death

Phospholipase A(2)s (PLA(2)s) represent a family of esterases that hydrolyze the sn-2 ester bond in phospholipids, releasing free fatty acids and lysophospholipids. PLA(2)s are important in the signaling of several cellular processes and are known to play a significant role in inflammation. Studies also show that PLA(2)s are modulators of drug-, chemical-, and ischemia/reperfusion-induced cellular injury. The role of PLA(2)s in apoptosis and oncosis depends upon the PLA(2) isoform, the cell type, and the stimulus of injury. The purpose of this review is to discuss the functions of iPLA(2), cPLA(2) and sPLA(2) isoforms in oncosis and apoptosis, including oxidant-induced and receptor-mediated cell death. In addition, the measurement and modulation of PLA(2) is discussed.     

Lipoprotein-associated phospholipase A2 activity is a marker of small, dense LDL particles in human plasma

BACKGROUND: Recent clinical studies showed that lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA(2) activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA(2) could be a marker of sdLDL in human plasma. METHODS: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA(2) activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA(2)). Non-HDL-Lp-PLA(2) activity and mass were calculated by subtracting the HDL-Lp-PLA(2) from total plasma Lp-PLA(2). RESULTS: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions < or =0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA(2) mass, total plasma Lp-PLA(2) activity and non-HDL-Lp-PLA(2) activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDL-Lp-PLA(2) activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non-HDL-Lp-PLA(2) activity and mass, but not Lp-PLA(2) mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL particle size. In multiple regression analysis, total plasma and non-HDL-Lp-PLA(2) activities were the second best predictors of the presence of sdLDL particles in human plasma after serum triglyceride concentrations. At serum triglyceride concentrations >1.356 mmol/L, total plasma and non-HDL-Lp-PLA(2) activity added significantly to the prediction of the presence of sdLDL in plasma. CONCLUSIONS: Lp-PLA(2) activity, but not the enzyme mass, is a marker of sdLDL in human plasma.     

Phospholipase A2 group XV activity during cardiopulmonary bypass surgery

ObjectivesAll patients who undergo cardiopulmonary bypass (CPB) experience some degree of ischemia reperfusion injury (IRI). Severe IRI-induced acute kidney injury (AKI) occurs in approximately 1–2% of patients undergoing CPB. Previous studies using activity-based protein profiling of urine identified group XV phospholipase A2, PLA2G15/LPLA2, as potentially associated with patients who develop AKI post CPB. The present study examined urinary PLA2G15/LPLA2 activity during CPB and in the near postoperative period for associations with subsequent AKI development.Design & methodsSamples were collected in a nested case controlled cohort of 21 patients per group who either did (AKI) or did not (non-AKI) develop AKI post-operatively. Serum and urine samples from each patient before, during and after CPB were assayed for PLA2G15/LPLA2 activity.ResultsUrine activity significantly increased during the intra operative period. In contrast the activities in paired sera were markedly decreased during CPB. There was no correlation between the serum and urine activity levels of patients. There were no significant differences in activity levels of PLA2G15/LPLA2 in the urine or sera from patients that did and did not develop AKI.ConclusionsThe lack of correlation between serum and urine activity levels suggests that the rapid intraoperative increases in PLA2G15/LPLA2 activity may originate from the kidney and as such offer an intraoperative indicator of early renal response to CPB associated stressors.     

Performance evaluation of a new chemiluminescent cardiac troponin I assay

Cardiac troponin I is a marker for diagnosis of myocardial damage. Several immunoassays are currently available for determination of concentrations of troponin I in serum. We evaluated a chemiluminescent assay for troponin I using ACS:180 automated analyzer (Bayer Diagnostics). We compared our results with two other immunoassays using the OPUS Magnum (OPUS troponin I assay, Dade Behring) and AxSYM (microparticle enzyme immunoassay, Abbott) analyzers. The within-run and between-run CVs were less than 5% for all three levels of controls. The chemiluminescent assay for troponin I was linear up to a serum troponin I concentration of 50 ng/mL and the detection limit was 0.1 ng/mL of troponin. A good correlation between troponin I concentration measured by the chemiluminescent assay (y axis) and the microparticle enzyme immunoassay (MEIA) (x axis) was observed, although the concentrations of troponin I in individual specimens were approximately four times higher, when measured by the MEIA assay, than those measured by chemiluminescent assay. The correlation coefficient was 0.98 with the regression equation y = 0.22x + 1.125. We also observed a good correlation in troponin I concentrations obtained by the chemiluminescent assay (y axis) and OPUS troponin I assay (x axis). The correlation coefficient was 0.96 and the regression equation was y = 0.79x - 0.52. The correlation coefficient was 0.93 when we compared troponin I concentrations obtained by the OPUS assay (x axis) with the corresponding concentrations obtained by the MEIA assay (y axis). The corresponding regression equation was y = 0.25x + 3.5. We conclude that the chemiluminescent troponin I assay showed good analytical performance.     

Phospholipase A(2) and Lipids as Potential Modulators of c-Raf-1 Kinase

c-Raf-1 is a proximal serine/threonine kinase in the signaling cascade of many mitogens. The cellular mechanisms responsible for regulation of this kinase remain ill-defined. Although c-Raf-1-associated proteins have been identified, including Ras, none of these have been found to activate c-Raf-1 kinase in vitro. To evaluate whether arachidonic acid or one of its products is implicated in c-Raf-1 activation, c-Raf-1 activity was measured in LLC-PK(1) kidney epithelial cells overexpressing the 100 kDa phospholipase A(2) (PLA(2)). As compared to control neomycin plasmid transfected cells, the cells overexpressing PLA(2) had a greater activation of c-Raf-1 in response to A23187 and phorbol ester stimulation. To explore the possibility that c-Raf-1 activity may be modulated directly by lipids, the enzymatic characteristics of c-Raf-1 were determined, and the effects of various possible lipid modulators on c-Raf-1 activity were examined. The K(m) of c-Raf-1 for ATP and mitogen-activiated protein kinase kinase (MAPKK), the only known physiologic substrate of c-Raf-1, were 11.6 &mgr;M and 0.8 &mgr;M, respectively. Of 13 lipids or combinations of lipids tested, including arachidonic acid and several eicosanoids, only phosphatidylserine and diacylglycerol in the presence of CA(2+) (2.5 mM) increased c-Raf-1 kinase activity significantly. The increase (1.5-fold) was approximately two orders of magnitude less than the stimulation of protein kinase C by these lipids. c-Raf-1 kinase activity and immunoreactivity eluted on gel filtration at a predicted molecular mass of greater than 150 kDa, suggesting that active c-Raf-1 is part of a multimeric complex. The absence of immunoreactive Ras in the active fractions confirms that the interaction is not necessary to maintain c-Raf-1 in an active state. In conclusion, a product of PLA(2) may play a role, together with Ras and another unidentified cofactor, in activating c-Raf-1. This lipid mediator(s) may directly or indirectly regulate the activity of c-Raf-1, but the identity of the mediator and its mode of interaction with c-Raf-1 and its associated proteins remain unclear.