缺血性脑血管病患者颈内动脉斑块的形态学研究

目的　探讨缺血性脑血管病患者和对照组颈内动脉斑块的形态学差异。方法　对 8例有缺血性脑血管病症状的死者进行尸体解剖 ,并对其颈内动脉进行连续取材 ,光镜观察斑块形态 ,并通过图像分析系统对斑块内脂质大小、斑块纤维帽厚度进行测定。同时对 8例年龄相当的无缺血性脑血管病症状的死亡病例 ,做颈内动脉对照研究。选取部分稳定及不稳定斑块进行免疫组织化学染色 ,观察二者巨噬细胞含量的差异。结果　 8例缺血性脑血管病组共 12 1个颈内动脉取材块中 ,不稳定斑块占 2 1.5 % (2 6 12 1) ;而对照组 10 9个颈内动脉取材块中不稳定斑块仅占11.0 % (12 10 9)。差异有显著性意义 (P <0 .0 1)。纤维帽厚度在有症状组和无症状组分别为 (0 .3± 0 .2 )mm和(0 .5± 0 .3)mm ,差异有显著性意义 (P <0 .0 1)。免疫组织化学显示不稳定斑块中巨噬细胞数量明显多于稳定斑块。结论　缺血性脑血管病患者颈内动脉斑块破裂与血栓形成的机会增加 ,斑块脂质中心越大 ,斑块表面纤维帽越薄 ,巨噬细胞越多 ,则斑块越不稳定 ,越容易破裂导致缺血性脑血管病症状的发生。     

缺血性脑血管病患者颈内动脉狭窄程度的观察

通过尸检材料对缺血性脑血管病病人颈内动脉进行研究 ,探讨颈内动脉狭窄程度和斑块内脂质含量与缺血性脑血管病发生的关系。 10例脑血管病病人生前均有缺血性脑血管病病史 ,死后尸检将颈内动脉颅外段完整剥离 ,固定后每隔 4mm取材并切片 ,然后光镜观察并通过计算机图象分析测定管腔的横截面积和斑块内脂质坏死中心的面积。 10例对照组病人生前均无缺血性脑血管病病史 ,研究方法和测量指标同上。结果发现 ,10例缺血性脑血管病组颈内动脉共 15 1个组织块中 ,管腔最大横截面积为 6 .2mm2 ,最小为 3.2mm2 ,平均为 4 .7± 0 .3mm2 。而对照组 134个组织块中 ,管腔最大横截面积为 6 .5mm2 ,最小面积为 3.6mm2 ,平均 4 .8± 0 .4mm2 ,两组比较无显著性差异。斑块内脂质坏死中心的平均面积在有症状组和对照组分别为 3.4± 0 .4mm2 和 1.8± 0 .2mm2 ,差异显著(P <0 .0 1)。另外 ,有症状组 11个斑块表面可见血栓 ,而对照组无血栓形成。结果表明 :缺血性脑血管病病人颈内动脉狭窄程度与对照组比较无明显差别 ,但斑块内脂质坏死中心却明显比对照组大 ,提示狭窄程度可能并非脑缺血症状的主要原因。斑块脂质坏死中心的大小可能起重要作用。     

基质金属蛋白酶在糖尿病患者动脉粥样硬化斑块中的表达

目的检测2型糖尿病患者动脉粥样硬化斑块内基质金属蛋白酶2(MMP2)和基质金属蛋白酶9(MMP9)的表达和分布,探讨MMP2和MMP9在糖尿病动脉粥样硬化斑块中表达的作用.方法从23例糖尿病足截肢和17例尸检下肢动脉标本中选取晚期动脉粥样硬化病变的组织126块,糖尿病组(74块),非糖尿病组(52块),从中随机选取各40块进行MMP2和MMP9抗原抗体的免疫组织化学染色,观察阳性物质在两组动脉粥样硬化斑块中的分布特点,利用计算机图像分析系统对染色程度作相对定量分析. 结果抗MMP2、抗MMP9免疫沉积物主要集中在斑块核心周围,特别是在斑块的肩部和纤维帽.糖尿病组动脉内膜抗MMP2免疫沉积物表达显著高于非糖尿病组[免疫沉淀物积分吸光度值(IA)69 014±14 459和57 004±16 171,阳性面积百分比(12.97±2.67)% 和(11.08±3.32)%,P<0.05];糖尿病组斑块内MMP9表达也显著高于非糖尿病组[IA 102 485±20 431和75 280±13 106,阳性面积百分比(18.35±3.59)%和(13.65±2.29)%,P<0.01]. 结论 MMP2和MMP9在糖尿病组动脉粥样硬化斑块中的表达显著高于非糖尿病组,MMP2和MMP9在糖尿病患者动脉中表达增强可以部分解释糖尿病患者易于发生动脉粥样硬化斑块破裂.     

光学相干断层成像技术评价动脉粥样硬化斑块

目的　应用光学相干断层成像（OCT）技术评价动脉粥样硬化斑块纤维帽厚度及其结构特征。方法　24只雄性新西兰大白兔,应用球囊拉伤加高脂饲养的方法制作动脉粥样硬化模型,动物随机分为两组：治疗组（n12）和对照组（n12）。对照组给予高脂饲料喂养,共22周;治疗组前10周给予高脂饲料喂养,后12周改为普通饲料喂养同时给予阿托伐他汀2　mg/（kg·d）。应用OCT评价血管管腔面积、管腔偏心指数、斑块纤维帽厚度及视频密度。22周处死动物后取靶血管行HE染色。结果　24只动物在第10周末OCT检查可见动脉粥样硬化斑块。第22周时治疗组管腔面积显著大于对照组（2.07±0.48　mm²比1.50±0.52　mm²,P0.016）,管腔偏心指数小于对照组（18.74%±9.28%比27.35%±7.21%,P0.025）。对照组斑块纤维帽厚度小于治疗组,但无统计学差异（70.00±26.08　μm比94.55±29.79　μm,P0.053）。分析OCT图像的视频密度显示,22周时对照组斑块纤维帽视频密度显著低于治疗组（49.7±7.5比59.4±4.3,P0.004）,相关性分析显示斑块纤维帽视频密度与细胞数量存在线性关系（R0.706,P0.001）。结论　OCT能精确评价动脉粥样硬化斑块纤维帽厚度变化,图像视频密度可用于反应斑块纤维帽结构特征。     

动脉粥样硬化斑块中的细胞凋亡及Bax/Bc1-2的基因表达

目的 探讨细胞凋亡与Bax/Bc1-2基因表达的内在联系,以及该基因表达与动脉粥样硬化斑决稳定性的关系.方法 选取人体动脉内膜剥脱术标本13例,固定、脱钙、每隔4 mm连续取材153块,常规HE染色,将斑块分为稳定斑块组和不稳定斑块组.每组40块并进行免疫组织化学染色.通过图像分析系统对各阳性区域进行半定量分析.结果 不稳定斑块组和稳定斑块组caspase-3、Bax、Bc1-2阳性细胞面积百分比分别为27.4%和15.4%(P＜0.05)、20.9%和15.1%(P＜0.05)、5.9%和10.3%(P＜0.01);纤维帽中巨噬细胞的面积百分比分别为17.3%和9.8%(P＜0.01),而平滑肌细胞的面积百分比分别为9.8%和15.9%(P＜0.05).结论 不稳定斑决较稳定斑块炎性反应严重,细胞凋亡率较高,细胞凋亡在不稳定斑块形成中起一定作用,Bax/Bc1-2参与了斑块内的细胞凋亡,be1-2在抑制斑块进展方面可能起一定作用.     

糖尿病患者动脉粥样硬化斑块内基质金属蛋白酶2和9与斑块稳定的关系

目的　比较糖尿病患者与非糖尿病组患者动脉粥样硬化斑块内基质金属蛋白酶 2和基质金属蛋白酶 9表达的差异 ,初步探索基质金属蛋白酶 2和基质金属蛋白酶 9与糖尿病动脉粥样硬化斑块稳定的关系。方法　从2 3例糖尿病足截肢和 17例尸检下肢动脉标本中选取晚期动脉粥样硬化病变的组织块共 12 6块 ,分为糖尿病组 (74块 )和非糖尿病组 (5 2块 ) ,从中随机选取各 4 0个组织块 ,运用免疫组织化学染色法检测基质金属蛋白酶 2和 9在两组粥样硬化斑块中的表达。结果　糖尿病组抗基质金属蛋白酶 2、抗基质金属蛋白酶 9免疫沉积物主要集中在斑块核心周围 ,特别是在斑块的肩部和纤维帽。糖尿病组动脉斑块内抗基质金属蛋白酶 2免疫沉积物表达显著高于非糖尿病组 (免疫沉淀物积分光密度值分别为 6 90 14± 14 4 5 9和 5 70 0 4± 16 171,阳性面积百分比分别为 13.0 %± 2 .7%和 11.1%± 3.3% ) ;糖尿病组斑块内基质金属蛋白酶 9表达也显著高于非糖尿病组 (免疫沉淀物积分光密度值分别为 10 2 4 85± 2 0 4 31和 75 2 80± 1310 6 ,阳性面积百分比分别为 18.4 %± 3.6 %和 13.7%± 2 .3% )。结论　基质金属蛋白酶 2和 9在糖尿病组动脉粥样硬化斑块中的表达显著高于非糖尿病组。基质金属蛋白酶 2和 9在糖尿病动脉中表达增     

冠脉斑块稳定性与肿瘤坏死因子相关研究

目的 探讨肿瘤坏死因子(Tumor necrosis fac-tor-alpha,TNF-α)与冠状动脉粥样硬化斑块稳定性的相关性。方法 以血管内超声(Intravascular Ultrasound,IVUS)检出冠状动脉粥样硬化斑块的软硬特性,通过临床是否为急性冠脉综合征患者,将具有软斑块特性,同时急性冠脉综合征者分为不稳定斑块组;而硬斑块特性,且不符合急性冠脉综合征者为稳定斑块组。测定两组间冠状窦及外周血血浆TNF-α浓度,结果与IVUS测定的斑块大小、斑块纤维帽厚度、脂核或无回声带大小、脂核或无回声带/斑块比及面积狭窄率进行相关性分析。结果 不稳定斑块组TNF-α值明显高于稳定斑块组[(o.11o±O.045)ng/mL vs(0.097±0.137)ng/mL,P<0.01和(0.111±0.037)ng/mL vs(0.042±0.022)ng/mL,P<0.05;将测得TNF-α与IVUS所测得纤维帽厚度、脂核或无回声带大小、斑块大小、脂核/斑块、面积狭窄率等进行相关分析,未见明显相关。结论TNF-α与斑块的稳定性有关,同时其在冠状循环与体循环中的量无差异,可望作为冠脉斑块不稳定性的判定指标。     

脂蛋白相关磷脂酶A2在颈动脉粥样硬化和缺血性卒中中的作用

脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2,Lp-PLA2)是磷脂酶A2超家族的一个亚型,主要由巨噬细胞和淋巴细胞产生.Lp-PLA2选择性水解低密度脂蛋白颗粒表面的氧化型磷脂,产生溶血磷脂胆碱和氧化型游离脂肪酸.Lp-PLA2表达于动脉粥样硬化斑块和不稳定斑块纤维帽内的巨噬细胞.研究表明,缺血性卒中患者血浆Lp-PLA2活性显著增高,而Lg-PLA2可能成为预测缺血性脑血管事件的独立危险因素.选择性LP-PLA2抑制剂可减轻炎症反应,增强斑块稳定性,抑制动脉粥样硬化斑块形成,有可能成为抗动脉粥样硬化斑块形成的一类新型药物.     

血凝素样氧化低密度脂蛋白受体-1与急性冠状动脉综合征关系的研究进展

探讨不稳定斑块形成、斑块破裂及急性冠状动脉综合征发生的机制对临床防治急性冠状动脉综合征有重要的指导意义。研究证实血凝素样氧化低密度脂蛋白受体-1作为氧化低密度脂蛋白的主要受体,介导了氧化低密度脂蛋白诱导的细胞凋亡、炎症反应、基质降解及血栓形成等过程,血凝素样氧化低密度脂蛋白受体-1表达增加会引起纤维帽变薄、脂核增大、斑块不稳定及破裂,最终导致急性冠状动脉综合征的发生。     

PROCR基因多态性与颈动脉斑块纤维帽变薄或破损相关性

目的研究PROCR基因多态性位点rs867186与中国人群缺血性脑卒中患者颈动脉斑块纤维帽厚薄及完整性的关系。方法前瞻性纳入本院收治的缺血性脑卒中患者,采集人口统计学资料及脑卒中风险因素等临床信息,颈动脉高分辨磁共振(MRI)判断颈动脉粥样硬化斑块纤维帽厚薄,依据纤维帽厚度及完整程度对纳入患者进行分组。利用Real-time PCR方法,使用Taq Man探针对厚/完整型纤维帽组及薄/破损型纤维帽组患者PROCR基因多态性位点rs867186进行基因分型。结果本研究共纳入176例缺血性脑卒中患者,其中95例颈动脉斑块具有厚/完整型纤维帽,81例具有薄/破损型纤维帽。对两组患者PROCR基因rs867186位点多态性分析显示,等位基因A是形成薄/破损型纤维帽斑块的风险因素(OR=2. 89,95%CI:1. 03～8. 06,P=0. 04),其基因频率在厚/完整型纤维帽组和薄/破损型纤维帽组中分别为91. 58%和96. 91%。结论 PROCR基因多态性位点rs867186与颈动脉粥样硬化斑块纤维帽变薄/破损相关。     

超声测量颈动脉内膜中层厚度与颈动脉斑块的关系

为了探讨颈动脉内膜中层厚度与局限性颈动脉斑块的联系 ,对 91名受试对象的颈总动脉内膜中层厚度及颈内动脉和颈动脉分叉处的斑块进行超声检测 ,并将颈动脉内膜中层厚度进行分级。结果观察到有斑块者较无斑块者其颈动脉内膜中层厚度明显增加 ( 0 .83± 0 .16mm比 0 .6 4± 0 .12mm ,P <0 .0 1) ,且随斑块的严重程度增加 ,其内膜中层厚度呈增厚趋势。该结果支持颈总动脉内膜中层厚度与颈动脉局限性动脉粥样硬化斑块明显相关 ,提示颈动脉内膜中层厚度增厚可能是颈动脉粥样硬化的早期表现     

高频体表超声检测急性冠状动脉综合征患者颈动脉结构及功能

应用高频体表超声观察急性冠状动脉综合征患者颈动脉结构及血管内皮功能的变化 ,探讨动脉粥样硬化结构和功能与急性冠状动脉综合征的关系。对 35例急性冠状动脉综合征患者检测了颈动脉粥样硬化斑块、内膜中膜厚度、肱动脉内皮功能的变化 ,并与 2 7例稳定型心绞痛及 31例正常对照组进行比较。结果发现 ,内膜中膜厚度和内皮依赖性血管舒张功能在急性冠状动脉综合征组 (分别为 0 .10± 0 .0 2和 3.98± 1.6 5 )和稳定型心绞痛组(分别为 0 .11± 0 .0 4和 4 .76± 2 .37)与对照组 (分别为 0 .0 7± 0 .0 1和 9.33± 3.4 7)有显著差异 (P <0 .0 5 ) ,斑块积分和斑块指数在急性冠状动脉综合征组 (分别为 4 .0 6± 2 .2 1和 3.14± 1.97)与稳定型心绞痛组 (分别为 4 .17± 1.76和3.2 1± 1.88)间无差异 (P >0 .0 5 ) ,急性冠状动脉综合征组颈动脉粥样硬化斑块以不稳定型为主。研究结果提示 ,外周血管超声检查可观察动脉粥样硬化病变 ,颈动脉结构及血管内皮功能与冠状动脉粥样硬化有关。     

短暂性脑缺血发作患者颈动脉斑块稳定性及其相关因素研究

目的 探讨短暂性脑缺血发作(TIA)患者颈动脉粥样硬化斑块稳定性及其相关危险因素.方法 对140例短暂性脑缺血发作患者行颈部血管超声及血液检查;根据颈部血管超声结果分为不稳定斑块组和稳定斑块组,比较两组间颈动脉粥样硬化斑块的稳定性及危险因素的差异.结果 不稳定组血清总胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、纤维蛋白原(FIB)、同型半胱氨酸(HCY)、性别、糖尿病史、吸烟与稳定组比较,差异有统计学意义(P＜0.05).TIA患者颈动脉粥样硬化斑块发生率84.29%.结论 TIA患者颈动脉粥样硬化斑块稳定性与CHOL、HDL-C、LDL-C、TG、HCY、FIB、性别、糖尿病史、吸烟有关,控制其危险因素有重要临床意义.     

Expression of NF-κB,CD68 and CD105 in carotid atherosclerotic plaque

Atherosclerotic plaque vulnerability is associated with cerebrovascular events in patients with carotid atherosclerosis. The aim of this study was to investigate the expression of inflammatory factors in carotid artherosclerotic plaques in order to explore its clinical significance in patients with carotid stenosis. Forty three patients with carotid stenosis were divided into symptomatic group (n=24) and asymptomatic group (n=19) based on clinical manifestation. All patients were treated with selective standard carotid endarterectomy (CEA); the carotid atherosclerotic plaques were removed surgically and studied pathologically to investigate the expression of nuclear factor-kappa κ (NF-κB), CD68 and CD105. The plaques were grouped into stable and unstable plaques based on thickness of the fibrous cap and the area of lipid-rich core in the plaques. The proportion of unstable plaques were significantly higher in symptomatic group than in asymptomatic group (70.8% vs. 63.2%, P=0.026). Results of immunohistochemisty staining showed that the expression of NF-κB, CD68 and CD105 in unstable plaques was higher than stable plaques (P<0.001). The association of the higher expression of these factors with instability of carotid plaque needs to be clarified in future study.KEYWORDS : Carotid stenosis, nuclear factor-kappa κ (NF-κB), CD68, CD105, vulnerable plaque     

Intravascular Palpography for High-Risk Vulnerable Plaque Assessment

BACKGROUND: The composition of an atherosclerotic plaque is considered more important than the degree of stenosis. An unstable lesion may rupture and cause an acute thrombotic reaction. Most of these lesions contain a large lipid pool covered by an inflamed thin fibrous cap. The stress in the cap increases with decreasing cap thickness and increasing macrophage infiltration. Intravascular ultrasound (IVUS) palpography might be an ideal technique to assess the mechanical properties of high-risk plaques. TECHNIQUE: Palpography assesses the local mechanical properties of tissue using its deformation caused by the intraluminal pressure. IN VITRO VALIDATION: The technique was validated in vitro using diseased human coronary and femoral arteries. Especially between fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012) was found. Additionally, the predictive value to identify the vulnerable plaque was investigated. A high-strain region at the lumen-vessel wall boundary has an 88% sensitivity and 89% specificity for identifying such plaques. IN VIVO VALIDATION: In vivo, the technique was validated in an atherosclerotic Yucatan minipig animal model. This study also revealed higher strain values in fatty than fibrous plaques (p < 0.001). The presence of a high-strain region at the lumenplaque interface has a high predictive value to identify macrophages. PATIENT STUDIES: Patient studies revealed high-strain values (1-2%) in thin-cap fibrous atheroma. Calcified material showed low strain values (0-0.2%). With the development of three-dimensional (3-D) palpography, identification of highstrain spots over the full length of a coronary artery becomes available. CONCLUSION: Intravascular palpography is a unique tool to assess lesion composition and vulnerability. The development of 3-D palpography provides a technique that may develop into a clinical tool to identify the high-risk plaque.     

陈旧性心肌梗死患者颈动脉粥样硬化与危险因素的关系

为探讨陈旧性心肌梗死患者颈动脉粥样硬化情况，对38例陈旧性心肌梗死患者的颈动脉内中膜厚度及斑块进行超声检测，与32例健康者作对照。结果发现，陈旧性心肌梗死患者的颈动脉内中膜厚度、斑块指数及斑块发生率明显高于对照组。多因素回归分析显示，年龄、总胆固醇、收缩压与颈动脉内中膜厚度密切相关。     

Velocity Vector Imaging of Longitudinal Mechanical Properties of Upstream and Downstream Shoulders and Fibrous Cap Tops of Human Carotid Atherosclerotic Plaque

Aims: Atherosclerotic plaque rupture is closely related to high regional mechanical stress in the plaque itself. We aimed to explore the longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human atherosclerotic plaques in vivo by velocity vector imaging (VVI) combined with acoustic densitometry (AD) imaging. Methods and Results: We included 135 patients with carotid atherosclerotic plaque. VVI and AD were used to examine 3 regions of carotid plaque along the longitudinal‐axis view. A total of 405 regions were classified with low or high AD values by corrected averages image intensity (AIIc%) < or ≥50, respectively. Peak systolic strain, strain rate (SR), and velocity were significantly greater for upstream than downstream shoulders and fibrous cap tops of carotid plaque (P < 0.05 for both). AIIc% was significantly lower for upstream than downstream plaque shoulders (P < 0.05). Peak systolic SR of the plaque regions was negatively correlated with corresponding AIIc% (R² = 0.499, P < 0.05). Conclusions: The longitudinal strain of human carotid atherosclerotic plaques as derived by VVI is associated with its corresponding AD but also in part with the internal position of the strain, with values greater for upstream than downstream shoulders and fibrous cap tops.     

A pathobiologic link between risk factors profile and morphological markers of carotid instability

ObjectiveAlthough cardiovascular risk factors have been strongly linked to carotid intimal-media thickness, their association with plaque progression towards instability is poorly understood.We evaluated a large database of endarterectomy specimens removed from symptomatic and asymptomatic patients to determine the correlation between major cardiovascular risk factors and carotid plaque morphology.MethodsIncidence of thrombotic, vulnerable and stable plaques together with the degree of plaque inflammatory infiltration was evaluated in 457 carotid atherosclerotic lesions. Clinical records were reviewed in all cases for risk factors profile.ResultsThrombotic plaques were more frequently observed in patients affected by stroke (66.9%) as compared to TIA (36.1%) and asymptomatic patients (26.8%, p < 0.001). Out of 457 carotid plaques removed during carotid endarterectomy, 181 (39.6%) were represented by thrombotic plaques, 72 (15.8%) by vulnerable plaques (thin cap fibroateroma) and 204 (44.6%) by stable plaques. At the multivariate analysis, a strong association was observed between hypertension, low HDL-cholesterol (HDL-C) and ratio of total to HDL-C >5 with vulnerable and thrombotic carotid plaques. Hypertension (p = 0.001), hypercholesterolemia (p = 0.05) and low HDL-C (p = 0.001) significantly also correlated with the presence of high inflammatory infiltrate of the plaque. When multivariate analysis was restricted to asymptomatic patients, hypertension (p = 0.009, OR 2.29), low HDL-cholesterol (p = 0.01 OR 2.21) and the ratio of total to HDL-C >5 (p = 0.03, OR 2.07) were confirmed to be the risk factors most significantly associated to unstable plaques. The relative risk to carry an unstable plaque for asymptomatic patients with high Framingham Risk Score as compared with those with low risk score was 2.06 (95% C.I., 1.26–3.36).ConclusionsThe present histopathological study identifies risk factors predictive of increased risk of carotid plaque rupture and thrombosis. Asymptomatic patients with high risk factors profile may constitute a specific target to reduce the likelihood of cerebrovascular accidents even in the presence of non-flow-limiting plaque.