老年下肢动脉粥样硬化在糖尿病患者中的病理特点

目的探讨老年糖尿病患者下肢动脉粥样硬化的病理特点.方法收集老年糖尿病尸体解剖病例8例,并设立对照组,将所有病例的两侧股动脉进行连续取材,常规病理检查,其中部分节段行α平滑肌肌动蛋白、CD68和bax染色.结果与对照组比较,糖尿病组股动脉粥样硬化程度更重,钙化范围更大;其斑块中的平滑肌细胞相对较少,巨噬细胞相对较多;bax在巨噬细胞的表达较多,在平滑肌细胞的表达减少.结论提示糖尿病可能促进了股动脉粥样硬化的发生、发展.     

细胞凋亡蛋白bax和下肢动脉粥样硬化的关系

目的探讨细胞凋亡蛋白bax和下肢动脉粥样硬化的关系。方法收集正常对照组股动脉标本12例(正常对照组)。糖尿病及非糖尿病尸检病例的股动脉标本各8例分别为糖尿病组及非糖尿病组。将所有动脉标本每隔4 mm连续取材,常规病理学检查,并行免疫组织化学染色。结果正常股动脉内膜未发现bax的表达。动脉粥样硬化病变的脂纹中可见巨噬细胞bax的表达。但平滑肌细胞上未发现bax表达。在斑块中,bax在平滑肌细胞和巨噬细胞均有表达。和非糖尿病组比较,糖尿病组斑块中bax阳性的平滑肌细胞多,bax阳性的巨噬细胞少。结论细胞凋亡蛋白bax参与下肢动脉粥样硬化的形成。糖尿病可能通过影响斑块中bax的表达,使斑块不稳定。     

老年患者股动脉粥样硬化的病理学特点与冠状动脉和颈动脉粥样硬化的比较

目的　探讨老年患者股动脉粥样硬化的病理学特点 ,并与同一个体的冠状动脉、颈动脉粥样硬化进行比较。方法　收集我院老年尸体解剖病例 15例。将所有病例之两侧股动脉、颈动脉及左冠状动脉前降支进行连续取材 ,光镜下观察三者动脉粥样硬化病变的形态学、病变分布情况 ,并对动脉粥样硬化程度进行评分。结果　在老年患者中 ,股动脉粥样硬化病变以晚期斑块尤其是复合病变为主 ,与颈动脉、冠状动脉粥样硬化相似。右股动脉的斑块检出率达 93.3%。与左冠状动脉前降支比较 ,股动脉和颈动脉粥样硬化的范围较小 ,程度较轻。三者在动脉粥样硬化程度和范围上无相关性。结论　股动脉和颈动脉粥样硬化可作为研究冠状动脉粥样硬化发生的间接指标。但在同一个体 ,不能用股动脉、颈动脉粥样硬化评估冠状动脉动脉粥样硬化的程度和范围。     

超声检测股动脉、腹主动脉及颈动脉粥样硬化与冠状动脉粥样硬化的相关性

目的:探讨股动脉、腹主动脉及颈动脉粥样硬化与冠状动脉粥样硬化的相关性。方法: 采用高频超声测量109例行冠状动脉造影术后1周的患者股动脉、腹主动脉及颈动脉的内-中膜厚度（IMT）、斑块积分及斑块数目。结果: 股动脉、腹主动脉及颈动脉粥样硬化与冠状动脉粥样硬化呈正相关（P<0.01、P<0.05）;股动脉斑块预测冠状动脉粥样硬化的灵敏度为89%,特异度为77%,准确度84%;腹主动脉斑块预测冠状动脉粥样硬化的灵敏度为73%,特异度为72%,准确度72%;颈动脉斑块预测冠状动脉粥样硬化的灵敏度为83%,特异度为79%,准确度82%。结论: 超声检查股动脉、腹主动脉及颈动脉IMT及斑块可间接预测不同程度的冠状动脉粥样硬化;股动脉的灵敏度与准确度较腹主动脉更好。     

人股动脉粥样硬化斑块内尿激酶型纤溶酶原激活物受体的表达

目的选用正常乳内动脉作为对照,分析人股动脉粥样硬化斑块中尿激酶型纤溶酶原激活物受体（uPAR）在不同部位的表达差异。方法从2005年9月至2006年2月,收集我院血管外科行股动脉粥样硬化斑块剥脱术中获取的血管内膜或内-中膜标本20例,以及心脏外科行冠状动脉搭桥术中的正常乳内动脉标本16例。通过免疫组织化学染色等方法,观察uPAR在斑块中的表达情况;明确uPAR与内膜巨噬细胞、平滑肌细胞的关系;同时半定量检测斑块不同部位uPAR表达量的差异。结果uPAR在正常乳内动脉的内膜和中膜未见表达,但在粥样硬化斑块内膜uPAR的平均光密度值（A）为92±37,明显高于中膜（46±28,P〈0．05）;内膜uPAR的积分光密度值（IA）较中膜升高约7倍（P〈0．01）。内膜uPAR表达定位于巨噬细胞、泡沫细胞和平滑肌细胞处,以平滑肌细胞与uPAR分布最为一致。斑块肩部、脂质池、破裂及血栓形成部位的uPAR IA值分别为42131±31671、45747±19963和55344±23069,均明显高于相对正常部位（5072±2588,P〈0．05）,其中在斑块破裂处表达量最高。结论人股动脉粥样硬化斑块的肩部、脂质池和破裂处,uPAR表达明显升高,提示uPAR可能在斑块破裂中起着重要作用。     

妊娠相关血浆蛋白-A及肿瘤坏死因子-α在人冠状动脉粥样斑块的表达及与斑块稳定性的关系

目的:研究妊娠相关血浆蛋白-A(PAPP-A)及肿瘤坏死因子-α(TNF-α)在人冠状动脉粥样斑块的表达及与斑块稳定性的关系.方法:从36例尸检标本中获得48个冠状动脉蜡块标本,其中急性心肌梗死15例,非急性心肌梗死的粥样硬化冠状动脉21例,由组织病理学分为稳定型(21个)和不稳定型(27个)斑块.采用免疫组织化学的方法测定巨噬细胞(CD68),平滑肌细胞(α-actin),PAPP-A及TNF-α在冠状动脉局部组织中的表达情况.结果:PAPP-A和TNF-α在血管内膜及中膜均有表达.PAPP-A在巨噬细胞及泡沫细胞处表达最明显.TNF-α阳性细胞见于斑块处的巨噬细胞、泡沫细胞、内皮细胞、平滑肌细胞及中膜平滑肌细胞胞浆.PAPP-A和TNF-α在不稳定型斑块内膜及中膜的表达均明显强于稳定型斑块(P<0.05).在不稳定型斑块处内膜PAPP-A与TNF-α表达强度呈正相关(r=0.744,P<0.001).结论:PAPP-A及TNF-α在冠状动脉粥样斑块局部有表达,在不稳定型斑块的表达明显高于稳定型斑块,与斑块的稳定性密切相关.PAPP-A在粥样斑块的表达与TNF-α呈正相关.     

超声新技术在颈动脉粥样硬化斑块评估中的研究进展

颈动脉粥样硬化斑块与缺血性卒中和冠状动脉疾病的发生密切相关,研究表明颈动脉粥样硬化斑块易损性是导致心脑血管疾病发生的主要原因之一,而颈动脉粥样硬化斑块易损性与其具有脂质坏死核心、薄纤维帽、巨噬细胞含量多以及斑块内出血等特点密切相关。超声具操作简易、成本低、安全性高以及费时少等优点,使其比其他成像方式更适合成为易损斑块的常规筛查方法。该综述主要介绍了几种有希望应用于检测颈动脉粥样硬化斑块易损性临床实践的新兴超声技术,及其便捷性和有效性。     

巨噬细胞、血管平滑肌细胞与冠状动脉粥样硬化易损斑块的相关性研究

冠状动脉动脉粥样硬化是冠心病的病理基础,以血管壁斑块形成为特征.易损斑块定义为易于导致血栓形成或能迅速发展为罪犯病变的所有斑块,其最常见的组织学亚型具有薄纤维帽(厚度＜65μm)、大脂核(脂质池体积＞40％)、大量巨噬细胞浸润(显微镜下＞25个/0.3mm直径)以及血管正性重构等特点.研究表明,65％～70％的血栓南薄纤维帽粥样硬化斑块引起[1],它的破裂是急性冠脉综合征的发病基础.冠状动脉动脉粥样硬化的各种发病机制均与巨噬细胞和血管平滑肌细胞有紧密关系.在易损斑块中,这两种细胞成分明显有别于稳定斑块以及正常血管,主要表现为:(1)较多巨噬细胞浸润;(2)纤维帽中的血管平滑肌细胞及其分泌的细胞外基质(包括胶原纤维和蛋白多糖等)均明显减少[2].冠状动脉粥样硬化斑块的易损性与这两种细胞密切相关,故深入研究有助于认识易损斑块的发生机制并积极进行预防干预.我们就巨噬细胞和血管平滑肌细胞与冠状动脉粥样硬化易损斑块的相关性进行简要综述.     

二维超声检测冠心病患者颈动脉粥样硬化病变

对103例经选择性冠状动脉造影的患者作双侧颈动脉超声检查，探讨了颈动脉超声检查的方法学以及颈动脉粥样硬化斑块的好发部位和超声分型，发现颈动脉粥样硬化斑块好发于颈动脉分叉处，以左侧多见，且多为扁平斑；颈动脉粥样硬化与冠状动脉粥样硬化之间有着密切的相关关系，冠状动脉病变支数越多，其颈动脉粥样硬化斑块积分也越高，不同冠状动脉病变组之间有非常显著的差异（P＜0．001）。     

老年脑梗死患者血浆MMP-9、CD105和TIMP-1的表达水平及其与颈动脉粥样硬化斑块稳定性的相关性

目的探讨老年脑梗死患者血浆中基质金属蛋白酶(MMP)-9、CD105及基质金属蛋白酶组织抑制剂(TIMP)-1的表达及其与颈动脉粥样硬化斑块稳定性的相关性。方法选择60例老年脑梗死患者为研究组,同期60例健康体检者为对照组,采用酶联免疫吸附法测定血浆MMP-9、CD105及TIMP-1的表达水平,颈动脉彩色多普勒超声检查患者颈动脉粥样硬化斑块稳定性,并行相关性分析。结果研究组患者的颈动脉粥样硬化斑块检出率86.67%明显高于对照组28.33%(c~2=41.773,P=0.000)。研究组患者的血浆MMP-9表达水平明显高于对照组,而CD105、TIMP-1表达水平明显低于对照组(P<0.01)。不稳定斑块组患者的血浆MMP-9表达水平明显高于对照组,而CD105、TIMP-1表达水平明显低于稳定斑块组(P<0.01)。相关性分析显示血浆MMP-9表达水平与颈动脉粥样硬化斑块稳定性呈正相关(r=0.305,P<0.05),CD105、TIMP-1表达水平与颈动脉粥样硬化斑块稳定性呈负相关(r=-0.336、-0.371,P<0.05),老年脑梗死患者血浆MMP-9、CD105及TIMP-1的表达与颈动脉粥样硬化斑块稳定性密切相关(P<0.05)。结论老年脑梗死患者颈动脉粥样硬化斑块发生率增高,血浆MMP-9水平升高,与颈动脉粥样硬化斑块稳定性正相关,CD105和TIMP-1降低与颈动脉粥样硬化斑块稳定性负相关。     

老年患者不同部位动脉粥样硬化斑块稳定性的相关性分析

目的探讨老年患者不同部位动脉粥样硬化（AS）斑块稳定性的相关性。方法对15例老年尸解者的股动脉、颈总动脉及左冠状动脉前降支进行连续取材,常规行病理检查;并选取部分节段行平滑肌肌动蛋白（SMA）、CD68、bax免疫组化染色;分析不同部位AS斑块中SMA、CD68、bax表达的相关性。结果三种AS斑块在SMA、CD68、bax表达方面均无相关性（P均〉0.05）。结论对老年患者不同部位的AS斑块稳定性及药物疗效评估等应分别进行监测。     

Significance of peptidoglycan,a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques

Peptidoglycan (PG) is a major component of the cell wall of gram-positive bacteria that is abundantly present in all human mucosa. PG is a functional lipopolysaccharide analog that binds to CD14 on macrophages and induces proinflammatory cytokine production and metalloproteinases. We investigated the hypothesis that bacterial PG is present in atherosclerotic tissue. In addition, plaque phenotypes were characterized in relation to presence of PG. Immunohistology of carotid (n = 15) and femoral (n = 6) endarterectomy specimens revealed the presence of PG in the cytoplasm of cells located in plaques. PG was detected in 14 of 15 carotid arteries and 5 of 6 femoral arteries. From the 14 coronary arteries, 31 atherosclerotic segments were selected. PG was detected within 19 of 31 of these coronary segments. Western blot demonstrated the presence of the toll-like receptor (TLR-2), the co-receptor for PG, in coronary artery tissue. The number of PG-containing cells in coronary arteries was significantly higher when the histologic features of plaque vulnerability were evident. Inflammation of the cap or shoulder was observed in 11 of 19 PG-positive versus 2 of 12 PG-negative segments (p = 0.023). More than 50% of the plaque area consisted of atheroma in 7 of 19 PG-positive segments and 0 of 12 PG-negative segments (p = 0.025). Heavy smooth muscle cell staining occurred in the plaque cap and shoulder in 3 of 19 PG-positive segments versus 9 of 12 PG-negative segments. Proinflammatory bacterial PG and its co-receptor have been observed in atherosclerotic arteries, in association with the vulnerable plaque phenotype.     

影像学检查对缺血性脑血管病患者颈动脉粥样硬化斑块的研究

目的采用双源CT血管造影(CTA)和高分辨MRI,探讨缺血性脑血管病患者颈总动脉分叉处粥样硬化斑块的性质、成分和动脉管腔狭窄程度与缺血性脑血管病的关系。方法选择缺血性脑血管病患者40例,经颈部CTA检测出颈总动脉分叉处粥样硬化斑块并伴管腔狭窄,再接受MRI扫描;分析颈动脉粥样斑块的性质、成分及管腔狭窄程度。结果 40例患者中,CTA检出斑块61个,其中混合性斑块31个;钙化性斑块18个;软斑块12个。高血压30例,检出斑块49个;无高血压10例,检出斑块12个。MRI检出斑块61个,其中Ⅲ型14个;Ⅳ～Ⅴ型23个,Ⅵ型6个;Ⅶ型18个。斑块内溃疡6例;颈动脉粥样硬化斑块造成同侧急性脑梗死14例,双侧颈动脉斑块造成双侧脑梗死10例,一侧颈动脉检出粥样斑块而对侧发生脑梗死2例。结论缺血性脑血管病患者颈动脉粥样硬化斑块主要以混合性斑块为主,双侧好发;高血压患者斑块发生率高于无高血压患者;颈动脉粥样硬化斑块造成同侧脑梗死发生率较高。     

Apoptosis in atherosclerosis: beneficial or detrimental?

Several groups have demonstrated apoptotic cell death in atherosclerotic plaques. The significance of apoptosis in atherosclerosis depends on the stage of the plaque, localization and the cell types involved. Both macrophages and smooth muscle cells undergo apoptosis in atherosclerotic plaques. Apoptosis of macrophages is mainly present in regions showing signs of DNA synthesis/repair. Smooth muscle cell apoptosis is mainly present in less cellular regions and is not associated with DNA synthesis/repair. Even in early stages of atherosclerosis smooth muscle cells become susceptible to undergoing apoptosis since they increase different pro-apoptotic factors. Moreover, recent data indicate that smooth muscle cells may be killed by activated macrophages. The loss of the smooth muscle cells can be detrimental for plaque stability since most of the interstitial collagen fibers, which are important for the tensile strength of the fibrous cap, are produced by SMC. Apoptosis of macrophages could be beneficial for plaque stability if apoptotic bodies are removed. Apoptotic cells that are not scavenged in the plaque activate thrombin which could further induce intraplaque thrombosis. It can be concluded that apoptosis in the primary atherosclerosis is detrimental since it could lead to plaque rupture and thrombosis. Recent data of our group indicate that apoptosis decreases after lipid lowering which could be important in our understanding of the cell biology of plaque stabilization.     

The role of ultrasonography of the peripheral arteries in diagnosing coronary artery disease

Atherosclerosis develops simultaneously in multiple arterial beds, that creates opportunity to diagnose of coronary artery disease. Aim of the study was the evaluation of association between atherosclerotic involvement of peripheral arteries assessed by ultrasound and significant coronary artery disease revealed by angiography. Study included 410 patients, (73% males), mean age 56.0 +/- 9.5 year scheduled for coronary angiography. During ultrasound examination of common carotid and common femoral arteries arterial wall intima-media (IMT) thickness and atherosclerotic plaques presence were assessed. Significant coronary artery disease (CAD) was diagnosed with coronary angiography as diameter stenosis > 50%. Intimo-media thickness (IMT) of common carotid arteries did not differ between groups with and without significant coronary artery disease (right 6.6 vs 6.4 mm, p = ns, left 6.9 vs 6.6 mm, p = ns) but in common femoral arterial was greater in patients with coronary artery disease (right 8.2 vs 7.1 mm, p < 0.005, left 7.9 vs 7.1 mm, p = 0.03). Atherosclerotic plaques in carotid and femoral arteries was detected more often in CAD patients (90.1% vs 34.6%, p < 0.0001). Positive predictive value for CAD diagnosis with detection of plaque in carotid or femoral artery was 93% and negative prognostic value for exclusion CAD after plaque exclusion in all arteries was 61%. Search for atherosclerotic plaques in ultrasound examination of peripheral arteries may facilitate CAD diagnosis in selected patients groups.