脑梗死血浆正五聚蛋白3的动态改变及与颈动脉不稳定斑块的关系

目的研究急性缺血性脑卒中与血浆正五聚蛋白3(pentraxin 3,PTX3)水平的关系,并探索血浆PTX3水平与颈动脉粥样硬化的关系。方法纳入急性缺血性脑卒中患者共103例,对照组患者83例。应用酶联免疫吸附法(ELISA)检测所有患者入院时的血浆PTX3水平,以及急性缺血性脑卒中患者规律治疗第7天的血浆PTX3水平。对急性缺血性脑卒中患者进行颈部多普勒血管超声检查,根据颈动脉斑块稳定性将患者分为两组。研究血浆PTX3水平与急性缺血性脑卒中及颈部斑块稳定性之间的关系。结果 (1)急性缺血性脑卒中组的血浆PTX3水平明显高于对照组(P0.05),经规律治疗7 d后,恢复期的血浆PTX3水平明显低于急性期(P0.05),但仍高于对照组(P0.05)。经多因素Logistic回归后提示血浆PTX3水平与急性缺血性脑卒中密切相关(OR=15.043,95%CI:3.46~65.45,P0.001)。(2)急性缺血性脑卒中组中,不稳定斑块组急性期和恢复期的血浆PTX3水平均高于无斑块与稳定斑块组(P0.05)。结论急性缺血性脑卒中患者具有较高的血浆PTX3水平,伴有颈动脉不稳定斑块的急性缺血性脑卒中患者血浆PTX3水平更高。血浆PTX3水平与急性缺血性脑卒中密切相关。     

血清正五聚蛋白3、超敏C反应蛋白水平与急性脑梗死患者的病情严重程度及预后的关系

目的 探讨急性脑梗死患者血清正五聚蛋白3(PTX3)和超敏C反应蛋白(hs-CRP)水平与急性脑梗死患者的病情严重程度及预后的关系。方法 选择发病24 h内急性脑梗死患者151例为脑梗死组,同时选取同期于本院体检健康人群103例为对照组; 检测和比较2组血清PTX3、hs-CRP水平; 比较NIHSS≥5分和NIHSS<5分的患者血清PTX3、hs-CRP水平以及mRS≤2分和mRS>2分患者的血清PTX3、hs-CRP水平; 分析血清PTX3、hs-CRP水平与急性脑梗死患者NIHSS评分和mRS评分的关系以及两者对于脑梗死的严重程度和预后的预测价值。结果 与对照组比较,脑梗死组急性期血清PTX3、hs-CRP水平均明显升高(P<0.05); 与脑梗死组NIHSS<5分患者比较,NIHSS≥5分患者急性期血清PTX3、hs-CR水平升高(P<0.05); 脑梗死组mRS>2分患者急性期血清PTX3、hs-CRP水平亦均高于mRS≤2分的患者(P<0.05); 急性脑梗死患者血清PTX3、hs-CRP水平与其 NIHSS和mRS得分均呈正相关(PTX3:r_s=0.471,0.451; hs-CRP:r_s=0.381,0.320; P<0.05); ROC曲线分析显示急性脑梗死患者急性期血清PTX3、hs-CRP水平对于脑梗死的严重程度和预后的预测价值均良好,但以血清PTX3水平预测脑梗死严重程度及预后的价值最优。结论 急性脑梗死患者急性期血清PTX3、hs-CRP水平与脑梗死的严重程度和预后均相关,且均对其预后的预测价值良好,但以血清PTX3水平的预测价值更优。     

血浆PTX3对动脉瘤性蛛网膜下腔出血后脑血管痉挛的预测价值

目的 分析血浆正五聚蛋白3(Pentraxin 3,PTX3)对动脉瘤性蛛网膜下腔出血后脑血管痉挛的预测价值。方法 收集本院2016年2月-2019年2月186例动脉瘤性蛛网膜下腔出血患者作为研究对象,经颅多普勒检测仪检测大脑中动脉(Middle cerebral artery,MCA)流速,MCA平均流速(Mean velocity of MCA,MCA Vm)>120 cm/s,且同侧Lindegaard≥3为血管痉挛组(92例),其余为无血管痉挛组(94例); 收集2组一般资料; 酶联免疫吸附(Enzyme linked immunosorbent assay,ELISA)法检测血浆中PTX3水平; 绘制受试者工作特性曲线(Receiver operator characteristic curve,ROC)分析血浆中PTX3对动脉瘤性蛛网膜者发生脑血管痉挛的诊断价值; 以血浆PTX3水平<4.73 ng/mL和≥4.73 ng/mL分为PTX3低表达组和PTX3高表达组,分析血浆PTX3水平与一般资料的关系; Logistic分析影响动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛的因素。结果 无血管痉挛组与血管痉挛组年龄、治疗方法、高血压病史、Fisher分级、Hunt-Hess分级存在明显差异(P<0.05); 与无血管痉挛组比较,血管痉挛组血浆PTX3水平升高(P<0.05); ROC曲线显示,血浆PTX3水平预测动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛的ROC曲线下面积为0.777,截断值为4.73 ng/mL,其敏感性为68.50%、特异性为74.50%; 血浆PTX3水平与年龄、治疗方法、Fisher分级、Hunt-Hess分级关系密切(P<0.05); Logistic分析显示,PTX3、年龄、Fisher分级、Hunt-Hess分级是影响动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛的独立危险因素。结论 动脉瘤性蛛网膜下腔出血脑血管痉挛患者血浆PTX3水平升高,PTX3对动脉瘤性蛛网膜下腔出血患者发生脑血管痉挛具有一定诊断价值。     

急性脑梗死患者糖原合成酶激酶-3β 正五聚蛋白3水平及意义

目的探讨糖原合成酶激酶-3β(GSK-3β)、正五聚蛋白3(PTX3)水平与急性脑梗死患者神经功能及血流动力学的相关性。方法选取2018-01—2019-12商丘市中心医院治疗的急性脑梗死患者110例为观察组,同时选取健康体检者100例为对照组,采用WB法检测血浆GSK-3β表达,采用免疫吸附法检测PTX3表达,检测脑循环血流速度、血流量和外周阻力。结果观察组外周血GSK-3β表达、PTX3明显高于对照组(P<0.05);观察组脑循环血流速度和血流量明显低于对照组(P<0.05),而外周阻力明显高于对照组(P<0.05);观察组NIHSS评分≥21分患者外周血GSK-3β表达、PTX3明显高于NIHSS评分<5分和5~20分患者(P<0.05);GSK-3β表达、PTX3与NIHSS评分呈正相关(r=0.592和0.444,P<0.05);GSK-3β表达、PTX3与脑循环外周阻力呈正相关(r=0.466和0.453,P<0.05)。结论急性脑梗死患者外周血GSK-3β、PTX3水平升高,与神经功能受损、脑循环外周阻力呈正相关。     

急性脑梗死患者血清sdLDL-C与PTX-3水平与颈动脉粥样硬化斑块性质的关系

目的通过联合测定血清小而密低密度脂蛋白胆固醇(sdLDL-C)、正五聚蛋白3(PTX3)水平探讨与急性脑梗死发生及颈动脉粥样硬化斑块性质的关系。方法纳入急性脑梗死患者150例为观察组,根据颈动脉粥样硬化斑块稳定性分为稳定型斑块组64例、易损斑块组86例,另取体检健康者102例为对照组。采用(ELISA)法检测血清sdLDL-C、PTX3水平。应用非条件多因素Logistic回归分析sdLDL-C、PTX3与急性脑梗死患者颈动脉粥样硬化斑块性质的关系。结果观察组血清sdLDL-C及PTX3水平明显高于对照组(P 0. 01);易损斑块组TG、LDL-C、sdLDL-C、PTX3均高于稳定斑块组(P 0. 01),但HDL-C水平低于稳定斑块组(P 0. 05);非条件多因素Logistic回归分析显示LDL-C、sdLDL-C、PTX3为急性脑梗死患者颈动脉粥样斑块稳定性的独立危险因素(P 0. 05)。结论血清sdLDL-C和PTX-3水平升高是急性脑梗死发生及不稳定颈动脉粥样硬化斑块形成的危险因素。     

Pentraxin-3的表达在脑卒中的研究进展

正出血性脑卒中(Hemorrhagic stroke,HS)起病急骤、病情凶险,具有较高病死率和不良预后率特征,目前还没有令人满意的药物治疗方法。PTX3(Pentraxin-3)是正五聚蛋白超家族中的一员,内皮细胞、平滑肌细胞、脂肪细胞、成纤维细胞、单核巨噬细胞及树突细胞等均可分泌PTX3,能反映血管的炎症状态,并与神经和血管再生有关,对脑卒中起功能性修复作用,可能成为治疗HS的新靶点。     

急性脑卒中患者血清PTX3、miR-199a的水平变化及临床意义

目的探讨急性脑卒中患者血清正五聚蛋白3(PTX3)、微小RNA-199a(miR-199a)的表达,分析二者与患者神经功能的关系及其对疾病的辅助诊断价值。方法选取2018年1月到2019年12月期间在我院接受治疗的急性脑卒中患者83例作为研究组,根据美国国立卫生研究院卒中量表(NIHSS)评分将患者分为轻度组(26例)、中度组(30例)、重度组(27例)。另选取同期在我院进行体检的志愿者40例作为对照组。检测所有研究对象血清中PTX3、miR-199a、中枢神经特异蛋白(S100-β)、神经元特异性烯醇化酶(NSE)的水平。结果研究组患者的血清PTX3、S100-β、NSE水平高于对照组,血清miR-199a水平低于对照组(P 0.05);重度组患者的血清PTX3、S100-β、NSE水平以及NIHSS评分高于中度组和轻度组,血清miR-199a水平低于中度组和轻度组(P 0.05),中度组患者的血清PTX3、S100-β、NSE水平以及NIHSS评分高于轻度组,血清miR-199a水平低于轻度组(P 0.05);经Pearson分析显示,急性脑卒中患者血清PTX3与S100-β、NSE、NIHSS评分均呈正相关(P 0.05),血清miR-199a与S100-β、NSE、NIHSS评分均呈负相关(P 0.05); ROC分析显示,血清PTX3、miR-199a对急性脑卒中均有一定的诊断价值,曲线下面积分别为0.864(95%CI 0.799～0.928)、0.807(95%CI 0.704～0.910),二者联合可进一步提高对急性脑卒中的诊断价值。结论急性脑卒中患者血清PTX3呈高表达,miR-199a呈低表达,且二者的表达均与患者的神经功能密切相关,二者对疾病均有一定辅助诊断价值。     

血清五聚素3、超敏C反应蛋白、脂蛋白相关磷脂酶A2水平以及微栓子信号与大动脉粥样硬化型急性脑梗死患者颈动脉粥样硬化斑块稳定性的相关研究

目的探讨血清五聚素3(PTX3)、超敏C反应蛋白(hs-CRP)、脂蛋白相关磷脂酶A2(LpPLA2)水平以及微栓子信号(MES)与大动脉粥样硬化型急性脑梗死患者颈动脉粥样硬化斑块稳定性的关系。方法依据中国缺血性卒中亚型分型(CISS),选取起病72 h内大动脉粥样硬化型急性脑梗死患者78例,使用二维彩色多普勒超声检测仪对颈动脉斑块的解剖和病理类型进行分析,将患者分为不稳定斑块组(40例)和稳定斑块组(38例),并同期从体检中心选取健康成人30名作为对照组。测定所有观察对象血清PTX3、hsCRP以及Lp-PLA2水平,分析各组间三种血液学指标水平的差异,并分别对三种血液学指标水平与颈动脉斑块稳定性进行相关性分析。对不稳定斑块组和稳定斑块组患者行TCD监测,分析两组之间MES检出率的差异。结果不稳定斑块组及稳定斑块组血清Hcy、hs-CRP、PTX3、Lp-PLA2水平及高血压的比例均明显高于对照组(均P0.05);不稳定斑块组他汀类用药史的比例明显高于对照组,血清PTX3、Lp-PLA2水平明显高于稳定斑块组(均P0.05)。不稳定斑块组的MES检出率显著高于稳定斑块组(P0.05)。Logistic回归分析显示,血清PTX3、Lp-PLA2水平是与斑块稳定性密切相关的影响因素(均P0.05)。血清PTX3水平预测斑块稳定性的ROC曲线下面积为0.963(P0.05),其临界值为2.57 ng/m L时,灵敏度为78.9%,特异度为84.2%。血清Lp-PLA2水平预测斑块稳定性的ROC曲线下面积为0.927(P0.05),其临界值为54.35μg/L时,灵敏度为72.9%,特异度为81.6%。结论血清PTX3、Lp-PLA2水平可能是预测颈动脉斑块稳定性的生物学指标。MES监测对于颈动脉斑块的稳定性评估具有一定的临床意义。     

动脉粥样硬化型ACI患者血清Lp-PLA2、MCP-1、VE-cadherin、PTX3变化及与IMT的关系

目的探讨动脉粥样硬化型(AT型)急性脑梗死(ACI)患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)、单核细胞趋化蛋白1(MCP-1)、血管内皮细胞钙黏蛋白(VE-cadherin)、五聚素3(PTX3)水平变化及其与颈动脉内-中膜厚度(IMT)之间的关系。方法选取AT型ACI患者104例(ACI组),根据ACI程度分为轻度组(n=46)、中度组(n=34)和重度组(n=24),根据颈动脉粥样硬化斑块(CASP)性质分为非CASP组(n=23)、CASP稳定组(n=38)与CASP不稳定组(n=43)。另选同期健康体检者40例为正常对照组(n=40)。测定并比较各组的血清Lp-PLA2、MCP-1、VE-cadherin、PTX3水平及与IMT的关系。结果 ACI患者的血清Lp-PLA2、MCP-1、VE-cadherin、PTX3水平及IMT显著高于对照组(P0.05),且随着病情程度加重呈显著增高趋势(P0.05),CASP稳定组和CASP不稳定组显著高于非CASP组,CASP不稳定组显著高于CASP稳定组(P0.05)。ACI患者的血清Lp-PLA2、MCP-1、VEcadherin、PTX3水平与IMT呈显著正相关性(均P0.05)。结论 AT型ACI患者具有明显IMT增厚及血清Lp-PLA2、MCP-1、VE-cadherin、PTX3高表达,且Lp-PLA2、MCP-1、VE-cadherin、PTX3水平与IMT厚度密切相关。     

正五聚蛋白3与缺血性卒中患者颈动脉狭窄的关系研究

目的 通过分析急性缺血性卒中患者血浆正五聚蛋白3（pentraxin 3，PTX3）和凝集素样氧化型低 密度脂蛋白受体-1（lectin-like oxidized low density lipoprotein receptor-1，LOX-1）与颈动脉狭窄的关系， 探索PTX3在颈动脉狭窄形成过程中的作用。 方法 前瞻性连续纳入2019年1-8月于首都医科大学附属北京友谊医院神经内科治疗的急性缺血 性卒中患者，收集患者的基线资料、头颅CTA、血脂、PTX3、LOX-1等检查结果。根据患者头颅CTA有无 颈动脉狭窄分为颈动脉狭窄组和无颈动脉狭窄组；以狭窄程度为标准，将颈动脉狭窄组患者分为严重 狭窄（≥50%）组和轻度狭窄（＜50%）组。采用单因素分析和多因素Logistic回归分析颈内动脉狭窄的 独立危险因素。 结果 共纳入102例患者，颈动脉狭窄组57例（55.9%），无颈动脉狭窄组45例（44.1%），颈动脉狭窄 组中轻度狭窄32例（56.1%），严重狭窄25例（43.9%）；颈动脉狭窄组的缺血性脑血管病家族史比例、 LDL-C、PTX3及LOX-1水平均高于无颈动脉狭窄组（均P <0.05）；严重狭窄组的PTX3、LOX-1及LDL-C水 平均高于轻度狭窄组（均P <0.05）。多因素Logistic回归分析结果显示PTX3（OR 3.11，95%CI 2.11～4.58， P =0.007）、LOX-1（OR 5.47，95%CI 2.89～10.13，P =0.017）和LDL-C（OR 5.35，95%CI 2.45～10.65， P =0.021）水平升高是颈动脉狭窄发生的独立危险因素。 结论 血浆PTX3、LOX-1和LDL-C水平升高是颈动脉狭窄的独立危险因素。     

Inducible expression of the long pentraxin PTX3 in the central nervous system

PTX3 is a prototypic long pentraxin consisting of a C terminal 203-amino acid pentraxin-like domain coupled with an N-terminal 178-amino acid unrelated portion. PTX3 is induced by primary proinflammatory signals in various cell types, most prominently macrophages and endothelial cells. Other long pentraxins, such as murine or rat neuronal pentraxin 1 (NP1) and human neuronal pentraxin 2 (NPTX2), are expressed in the central nervous system (CNS). The present study was designed to investigate whether PTX3 is expressed in the brain and to define the structures and cells involved. Intracerebroventricular (i.c.v.), but not i.v., injection of LPS induced high levels of PTX3 mRNA in the mouse brain. In contrast NP1 is constitutively expressed in the murine CNS and is not modulated by LPS administration. I.c.v. IL-1beta was also a potent inducer of PTX3 expression in the CNS, whereas TNFalpha was substantially less effective and IL-6 induced a barely detectable signal. Central administration of LPS and IL-1 induced PTX3 also in the periphery (heart), whereas the reverse did not occur. Expression of PTX3 was also observed in the brain of mice infected with Candida albicans (C. albicans) or Cryptococcus neoformans. (C. neoformans). The kinetics of PTX3 gene induction were consistently different between C. albicans- and C. neoformans-infected mice, according to the diverse outcome of the CNS immune reaction. In situ hybridization revealed that i.c.v. injection of LPS induced a strong PTX3 expression in presumptive glial cells, in the white matter (corpus callosum, fimbria) and meningeal pia mater as well as in dentate gyrus hilus and granule cells. No constitutive expression of PTX3 was detected. Central expression of PTX3 may amplify mechanisms of innate resistance and damage in the CNS. The possibility of a direct interaction of PTX3 with neuronal cells, as suggested for NPTX2, remains to be explored.     

Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke

Recent clinical studies suggest that pentraxin 3 (PTX3), which is known as an acute-phase protein that is produced rapidly at local sites of inflammation, may be a new biomarker of disease risk for central nervous system disorders, including stroke. However, the effects of PTX3 on cerebrovascular function in the neurovascular unit (NVU) after stroke are mostly unknown, and the basic research regarding the roles of PTX3 in NVU function is still limited. In this reverse translational study, we prepared mouse models of white matter stroke by vasoconstrictor (ET-1 or L-Nio) injection into the corpus callosum region to examine the roles of PTX3 in the pathology of cerebral white matter stroke. PTX3 expression was upregulated in GFAP-positive astrocytes around the affected region in white matter for at least 21 days after vasoconstrictor injection. When PTX3 expression was reduced by PTX3 siRNA, blood-brain barrier (BBB) damage at day 3 after white matter stroke was exacerbated. In contrast, when PTX3 siRNA was administered at day 7 after white matter stroke, compensatory angiogenesis at day 21 was promoted. In vitro cell culture experiments confirmed the inhibitory effect of PTX3 in angiogenesis, that is, recombinant PTX3 suppressed the tube formation of cultured endothelial cells in a Matrigel-based in vitro angiogenesis assay. Taken together, our findings may support a novel concept that astrocyte-derived PTX3 plays biphasic roles in cerebrovascular function after white matter stroke; additionally, it may also provide a proof-of-concept that PTX3 could be a therapeutic target for white matter-related diseases, including stroke.     

The acute-phase protein PTX3 is an essential mediator of glial scar formation and resolution of brain edema after ischemic injury

Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood–brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders.     

Hospital Mortality of Patients with Severe Traumatic Brain Injury is Associated with Serum PTX3 Levels

Background

Traumatic brain injury (TBI) is a worldwide cause of morbidity and mortality. Pentraxin 3 (PTX3) is a humoral component of the innate immune system which has been studied as a marker of inflammatory, infections or cardiovascular pathologies. To investigate the association between serum levels of PTX3 and the hospital mortality of patients with severe TBI.

Methods

The independent association between serum PTX3 levels after severe TBI (Glasgow Coma Scale, GCS ≤ 8) and hospital mortality was analyzed in a prospective study of 83 consecutive patients by a multiple logistic regression analysis. The leukocyte count in the same sample was analyzed as another marker of inflammatory response.

Results

The mean age of patients was 35 years and 85% were male. Serum PTX3 levels were determined 18.0 (SD ± 17.0) h after TBI. Patients who died showed a mean serum PTX3 level of 9.95 μg/ml (SD ± 6.42) in comparison to 5.46 μg/ml (SD ± 4.87) of the survivor group (P = 0.007). Elevated serum PTX3 levels remain significantly associated with mortality (P = 0.04) in the subset of patients with isolated TBI (n = 34). There were no differences in the leukocytes count measured in the same blood sample used for PTX3 determination in survivors and non-survivors (P = 0.56). The final multiple logistic regression model including age, pupillary examination, GCS, associated trauma, and PTX3 levels shows that serum levels of PTX3 which were higher than 10 μg/ml were independently associated with the patients mortality (adjusted OR 3.06, CI 95% 1.03–9.15, P = 0.04).

Conclusions

Serum PTX3 levels after severe TBI are independently associated with higher hospital mortality and may be a useful marker of TBI and its prognosis.