兔腹主动脉粥样硬化支架植入后血管壁及内膜改变

目的通过建立兔腹主动脉粥样硬化植入支架动物模型,探讨支架植入后血管壁和内膜变化及发生机制.方法采用兔腹主动脉内膜剥脱术加含1.5%高胆固醇的高脂饮食来建立动脉粥样硬化动物模型,并在此基础上建立兔粥样硬化腹主动脉植入支架模型,并通过组织病理学检查,来揭示支架植入后血管壁和内膜组织形态学变化和病变的发生机制.结果在动脉粥样的动物模型基础上所建立兔腹主动脉粥样硬化植入支架动物模型,经组织形态学和免疫组化检查显示:动物模型目标血管段管腔内膜明显增厚、血管出现不同程度的狭窄,新生内膜中有大量增殖细胞核抗原(PCNA)高表达(着色强度IS:5.268±0.475)的血管平滑肌细胞(VSMC)和泡沫细胞及细胞外基质(ECM).经计算机图像分析仪测定其组织形态学指标分别为残余管腔面积[(9.67±0.18)mm2]、最大内膜厚度[(1.33±0.05)mm]、内膜面积[(5.78±0.23)mm2]和狭窄程度[(31.02±1.91)%].结论本实验成功地建立了兔腹主动脉粥样硬化植入支架动物模型,并认为支架术后血管新生内膜中VSMC过度增殖是导致支架植入后管腔内膜明显增厚的可能原因.     

卡托普利、缬沙坦对兔动脉粥样硬化斑块的干预作用

目的观察高胆固醇饮食造成兔大动脉粥样斑块形成过程中卡托普利和缬沙坦对大动脉粥样斑块形成的干预作用。方法30只健康雄性新西兰兔随机分为高脂饮食组(A组),高脂饮食加卡托普利组(B组),高脂饮食加缬沙坦组(C组)和对照组(D组)喂养10周后,行超声检测腹主动脉内膜中膜的厚度。并行病理观察血管内膜以及血管内皮细胞情况。结果A组腹主动脉壁粥样斑块形成,血管内膜增厚;B组和C组血管壁有少量粥样斑块形成,血管内膜增厚均较A组明显减轻(P<0.01)。结论卡托普利和缬沙坦具有抗高胆固醇血症致动脉壁粥样斑块形成的确切效果。     

磁共振成像技术识别兔腹主动脉易损斑块的实验研究

目的探讨磁共振成像(MRI)识别动脉粥样斑块性质的价值。方法制作兔腹主动脉易损斑块模型,对兔腹主动脉分别采用MRI扫描,血管内超声(IVUS)检查和病理学检查。结果成功建立兔腹主动脉易损斑块模型。MR图像T_1WI、T_2WI、PDWI序列中易损斑块呈高信号,FSE-PDWZ脂肪抑制信号消失,SE T_1WI增强扫描可见斑块略有强化;稳定斑块的影像学表现为斑块厚度增大,以等信号居多,增强扫描后斑块强化明显;与病理切片结果符合率较高,与IVUS的结果相近。结论MRI可以检测兔腹主动脉粥样斑块并进行定性分析。     

高脂血症患者腹主动脉血流动力学改变与粥样硬化的关系

目的 研究高脂血症患腹主动脉血流动力学改变与粥样硬化之间的关系,评价血流动力学改变在腹主动脉粥样硬化形成中的作用。方法 对62例高脂血症患进行腹主动脉超声检查,并根据腹主动脉是否存在粥样斑块分为斑块组和无斑块组,测定其内径及峰值流速,计算最大剪切率。结果 斑块组患腹主动脉的峰值流速及最大剪切率明显低于无斑块组,年龄及收缩压明显高于无斑块组;两组患的舒张压、血脂、血糖水平及吸烟指数均无显性差异。结论 最大剪切率减低及年龄和收缩压的升高与腹主动脉粥样硬化的形成密切相关。     

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。     

艾赛布考抑制兔动脉粥样硬化的作用及可能机制

目的:艾赛布考是普罗布考代谢稳定的衍生物,具有抗氧化、抗炎、抗增殖特性。本研究旨在探讨艾赛布考对高胆固醇血症兔腹主动脉损伤后动脉粥样硬化发展的影响。方法:45只雄性新西兰兔随机分为对照组、艾赛布考组、普罗布考组3组,每组15只,分别给予高脂饮食(对照组),高脂饮食+1%艾赛布考(艾赛布考组)或1%普罗布考(普罗布考组),2周后,行腹主动脉内膜球囊损伤术,继续药物干预10周。12周末,行血管内超声评价三组兔腹主动脉粥样硬化斑块面积和斑块负荷;通过免疫组织化学法观察斑块内巨噬细胞的含量,免疫组织化学法、实时定量聚合酶链式反应分别检测斑块组织内炎症因子细胞间黏附分子-1、单核细胞趋化蛋白-1、基质金属蛋白酶-9蛋白及信使核糖核酸的表达。结果:与对照组相比,艾赛布考组兔血中低密度脂蛋白胆固醇及氧化应激水平显著降低,腹主动脉粥样硬化斑块内巨噬细胞含量及炎症因子表达也降低,斑块面积及斑块负荷显著减少(P均0.01)。与普罗布考组相比,艾赛布考组兔腹主动脉斑块面积及斑块负荷降低更加显著,差异具有统计学意义(P均0.01)。结论:艾赛布考通过调脂、抗炎、抗氧化作用,抑制内膜损伤后动脉粥样硬化进展。     

血管内超声在兔主动脉血管成形术后再狭窄诊断中的应用

目的 探讨血管内超声（IVUS）对兔经皮腔内血管成形术（PTA）后动脉粥样硬化模型血管再狭窄的诊断价值.方法 采用30只高脂喂养—球囊损伤新西兰兔胸腹主动脉建立动脉粥样硬化及PTA后再狭窄模型,分别于PTA术时及术后1、3、6个月行主动脉血管造影及IVUS显像检查,观察血管腔形态、狭窄度以及两种检查的相关性.结果 与PTA术前比较,PTA术后6个月IVUS以及血管造影检测到腹主动脉管腔明显狭窄（P≤0.05或P≤0.01）,IVUS检测到狭窄度较动脉造影组更为明显（P≤0.05）.IVUS对钙化斑块、偏心性斑块的检出率明显高于血管造影（P≤0.05）.结论 IVUS可准确测量血管腔的狭窄程度,确定血管腔内斑块的性质.     

超声声学造影诊断腹主动脉穿透性粥样硬化性溃疡的临床价值

目的探讨超声声学造影在诊断腹主动脉穿透性粥样硬化性溃疡的临床价值。方法对6例常规彩色多普勒超声检查怀疑腹主动脉穿透性粥样硬化性溃疡患者行超声声学造影检查,与CT血管造影检查结果进行对比。结果 6例患者中,超声声学造影和CT血管造影均显示,腹主动脉穿透性粥样硬化性溃疡4例,腹主动脉夹层2例。彩色多普勒超声检查显示6例均为腹主动脉穿透性粥样硬化性溃疡。与CT血管造影检查比较,单独使用彩色多普勒超声的符合率为66.7%,联合使用超声声学造影的符合率为100%。结论超声声学造影可以为腹主动脉穿透性粥样硬化性溃疡的诊断和鉴别诊断提供重要的影像学信息。     

颈动脉粥样硬化斑块与脑梗死关系的探讨

目的探讨颈动脉粥样斑块与脑梗死发生的关系。方法应用彩色多普勒超声对48例陈旧脑梗死患者检查颈动脉血流及粥样硬化(CAS)斑块形成情况,并与30名健康志愿者作为对照。观察两组研究对象血管狭窄和附壁粥样硬化斑块情况。结果48例脑梗死患者中,有颈动脉粥样硬化斑块者40例,占83．3%；对照组颈动脉管壁增厚及斑块形成10例,占33．3%,二者比较差异有非常显著性意义(P＜0．01)。结论脑梗死与颈动脉粥样硬化斑块有着密切关系,颈动脉彩色多普勒超声检查对颈动脉粥样硬化及斑块的检出有助于对脑梗死的预测和防治。     

超微血流显像与超声造影评价极低回声区斑块内新生血管分布的研究初探

目的:探讨超微血流显像(SMI)技术在评价存在局限性极低回声区(JBA)的颈动脉粥样硬化斑块内新生血管的价值。方法:选取存在JBA的颈总动脉及颈内动脉起始段的低回声或低回声为主的不均质斑块进行SMI和超声造影(CEUS)检查,对检查结果进行对比,评估这些斑块内的新生血管状况。结果:SMI和CEUS检查显示38例存在JBA的斑块内均可见新生血管。斑块厚度0.21～0.63cm,平均(0.38±0.10)cm;斑块长度0.90～5.2cm,平均(2.21±1.06)cm;SMI及CEUS显示斑块内新生血管分级为1～2级,但在JBA区域未见明显新生血管。结论:有JBA的颈动脉粥样硬化斑块内新生血管比率高,但新生血管并不在JBA区域内。     

原位杂交检测胰岛素样生长因子-1受体基因在动脉粥样硬化组织中的表达

为观察胰岛素样生长因子１受体基因在动脉粥样硬化组织中的表达及分布,建立实验性动脉粥样硬化家兔模型。采用人胰岛素样生长因子１受体ｃＲＮＡ探针进行组织原位杂交。结果发现,正常对照的家兔主动脉组织,仅在外膜显示有胰岛素样生长因子１受体ｍＲＮＡ的阳性表达,中膜及内膜均呈阴性;实验组主动脉的整个血管壁,包括外膜、中膜、新生内膜及动脉粥样硬化斑块组织均有胰岛素样生长因子１受体基因的表达。研究提示,增殖的血管平滑肌细胞、新生的内皮细胞及构成动脉粥样硬化斑块主要成分的泡沫细胞均为胰岛素样生长因子１受体ｍＲＮＡ表达的靶细胞,证实胰岛素样生长因子１受体基因参与动脉粥样硬化的发生。     

Changes in the proliferative activities of cells in experimental atherosclerotic plaques during remodeling

To investigate the relationship between cytologic alterations and cellular proliferation during atherosclerotic remodeling, we examined experimental atheromatous plaques by immunohistochemistry. Plaques were formed on rabbit aortas by cholesterol-enriched diets and mechanical stimulation over a period of 2 months. Plaques were examined 1 month and 6 months after induction. We used antibodies RAM-11, HHF-35, and monoclonal anti-proliferating cell nuclear antigen (PCNA) antibody for detection of macrophages (Mphi), smooth muscle cells (SMC), and PCNA, respectively. One month after induction, the plaques revealed a thickened intima with a fibrofatty histologic pattern or accumulation of foam cells. With either histologic pattern, foam cells were found to be Mphi and proliferative activity was mainly observed in Mphi. Six months after induction, calcification and organization were seen on the induced plaques, suggesting progression of remodeling. There were fewer Mphi and more SMC compared with plaques examined 1 month after induction. Proliferative activity was observed mainly in SMC. We have demonstrated that the proliferative activity of cell types changes during remodeling of atheromatous plaques. Our results suggest an important relationship between the proliferative activity of SMC and remodeling.     

The expression of angiotensin-I converting enzyme in human atherosclerotic plaques is not related to the deletion/insertion polymorphism but to the risk of restenosis after coronary interventions

Plasma and tissue concentrations of the angiotensin-I converting enzyme (ACE) have been shown to be associated with the ACE insertion/deletion (I/D) polymorphism. The purpose of this study was to examine the relation of ACE levels in atherosclerotic plaques to the ACE I/D polymorphism and to restenosis after balloon angioplasty and directional atherectomy (DCA). The study included 104 patients who underwent DCA and received angiographic follow-up at 12 to 18 months. The amount of ACE protein in various morphologically defined plaque components (fibrous, atheromatous, and complicated lesions) of the atherectomy specimens was determined by qualitative and semiquantitative immunohistochemistry. ACE levels were related to the ACE genotype, to plaque morphology and to the risk of restenosis. Sequential staining revealed that pathologic ACE overexpression of the atherosclerotic lesions occurred in intimal smooth muscle cells, fibrocytes/fibroblasts and macrophage/foam cells. The ACE content of the whole plaques and of the single plaque components was not associated with the I/D polymorphism, but with restenosis after coronary interventions. In addition, ACE levels in the atherosclerotic lesions correlated with the severity of vessel wall damage. The ACE phenotype might serve as an indicator for the risk of restenosis after coronary interventions.     

牛磺酸对兔动脉粥样硬化血管平滑肌细胞凋亡的影响

目的:探讨牛磺酸对兔动脉粥样硬化血管平滑肌细胞凋亡及凋亡相关基因bcl-2、bax和caspase-3蛋白表达的影响.方法:将24只日本大耳白兔随机分为正常对照组、高脂模型组和牛磺酸组,14周后观察各组主动脉组织病理形态学改变,透射电镜观察斑块内平滑肌细胞超微结构变化,流式细胞术检测动脉粥样斑块内平滑肌细胞凋亡率,免疫组化染色法检测凋亡相关基因bcl-2和bax蛋白表达,Western blot蛋白印记法检测caspase-3蛋白表达.结果:高脂模型组与正常对照组比较,动脉内膜出现典型的斑块,管腔极度狭窄,典型的凋亡平滑肌细胞明显增多,平滑肌细胞凋亡率、bax及caspase-3蛋白表达升高(P<0.01),bcl-2蛋白表达降低(P<0.05).牛磺酸组与高脂模型组比较,主动脉斑块缩小,动脉管腔狭窄减轻,凋亡平滑肌细胞不典型且较少,平滑肌细胞凋亡率、bax蛋白表达及caspase-3蛋白表达降低(P<0.01),bcl-2蛋白表达升高(P<0.05).结论:牛磺酸可能通过对bcl-2、bax及caspase-3蛋白表达的调控而降低动脉斑块内过度凋亡的平滑肌细胞,从而抑制粥样斑块的形成.     

Potential embolization by atherosclerotic debris dislodged from aortic wall during cardiac catheterization:: histological and clinical findings in 7,621 patients.

Embolic events during cardiac catheterization have been attributed to atherosclerotic aortic debris dislodged by catheter manipulation. We evaluated the frequency and the histologic morphology of atherothrombotic material retrieved during placement of coronary catheters in patients undergoing diagnostic or interventional cardiac procedures. Over a 4-year period, macroscopically visible aortic debris from coronary catheters, if present after advancement to the ascending aorta, was obtained for histologic examination. In 41 of 7,621 patients (0.54%), visible atherothrombotic material was present in the backflow of catheters. Debris occurred most frequently with 8 Fr guiding catheters (98%). Histologic examination showed foam cells, cholesterol crystals, and amorphic lipoid substance as markers of atheromatous material from atherosclerotic plaques in 38/41 patients (93%) with former plaque hemorrhage in 55% of them. In three patients, fresh thrombus material was observed (7%). None of these patients showed in-hospital ischemic complications. Although visible atheromatous material is a rare phenomenon in cardiac catheterization, an increased risk of scraping debris is associated with large-lumen guiding catheters. In order to avoid vascular embolization, the use of smaller guiding catheters and sufficient free backflow of catheters after advancement are recommended.     

Contrast enhancement of coronary atherosclerotic plaque: a high-resolution, multidetector-row computed tomography study of pressure-perfused, human ex-vivo coronary arteries

OBJECTIVES: The objective of this study was to investigate the effect of contrast injection on atherosclerotic coronary plaque attenuation measured using multidetector-row computed tomography. BACKGROUND: Recent multidetector-row computed tomography studies have described the characterization of coronary atherosclerotic plaque on the basis of Hounsfield unit values. The influence of contrast injection on the attenuation of individual plaque components, however, is unknown. METHODS: Using a pressurized perfusion system, 10 human coronary arteries were examined postmortem with multidetector-row computed tomography and histology. Pre-enhanced, peak-enhanced, and delayed enhanced multidetector-row computed tomography images were acquired during continuous perfusion of the vessel. A total of 37 focal atherosclerotic plaques were identified. Vessel wall attenuation was measured from multidetector-row computed tomography images during all three enhancement phases. On the basis of the histology, plaques were categorized as noncalcified (predominantly fibrous or predominantly fibrofatty), mixed calcified (calcified fibrous or calcified necrotic core), or densely calcified. The mean Hounsfield unit was compared among contrast phases for all plaques and in plaque subgroups. RESULTS: We observed contrast enhancement of atherosclerotic plaques within the vessel wall. For noncalcified plaques including both fibrous and fibrofatty plaques, the mean Hounsfield unit of the vessel wall during and after contrast injection exceeded the mean value before injection (t-test, P<0.002). CONCLUSION: The present study demonstrates that intra-arterial injection of iodinated contrast agent results not only in luminal enhancement but also in atherosclerotic plaque enhancement in pressure-perfused coronary arteries imaged ex vivo. Plaque enhancement should be considered when characterizing plaque components on the basis of Hounsfield unit with multidetector-row computed tomography.     

Modulation of arterial smooth muscle cells in culture and cholesterol exchange]

The phenotypic modulation and the enhanced proliferation of smooth muscle cells (SMC) as well as their foam transformation are major processes in arterial pathophysiology and during atherogenesis. Arterial SMC play a crucial role, in response to several stimuli: the SMC "activation" is an essential condition leading to the adult atherosclerotic plaque formation. Owing to the difficulty to study the SMC regulation in vivo, most of the literature in this field refers to in vitro models. Modulated SMC in culture, changing from a contractile to a synthetic state, share similar features with atherosclerotic plaques cells. The phenotypic modulation of SMC is expressed by morphological, biochemical, metabolic and functional modifications. The regulation of cholesterol movements might influence the foam transformation process of arterial SMC.     

依折麦布辛伐他汀片对兔腹主动脉粥样硬化斑块逆转作用的实验研究

目的：观察腹主动脉粥样斑块内炎性巨噬细胞和平滑肌细胞的表达情况,以探索依折麦布联合他汀类药物在逆转动脉斑块中的作用及机制。方法选取24只健康雄性新西兰大耳白兔,随机分为对照组（n＝8）和高胆固醇血症组（n＝16）。对照组给予普通饲料,喂养12周。高胆固醇血症组喂饲致动脉粥样硬化饲料（由普通颗粒饲料＋15g/L胆固醇＋100g/L猪油＋150g/L蛋黄粉组成）2周后行腹主动脉内膜球囊拉伤术,术后再随机分为模型亚组和依折麦布辛伐他汀（ES）亚组（给予5/10mg/（kg·d）每组8只,两亚组均继续喂饲致动脉粥样硬化饲料10周。喂养第12周时活杀动物,取腹主动脉进行石蜡切片。检测不同时间点脂质和脂蛋白,应用光学显微镜观察动脉粥样硬化进程,采用免疫组化方法分析巨噬细胞和平滑肌细胞在斑块处的表达。结果 ES亚组的血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）浓度明显低于模型亚组（P＜0.01）。病理检测显示两亚组及ES亚组斑块直径、斑块厚度和动脉内/中膜厚度经单因素方差分析,差异有统计学意义（P＜0.05）。免疫组化检测结果示ES亚组血管壁中巨噬细胞的表达量较模型亚组显著减少（P＜0.05）,而平滑肌细胞的表达量较模型亚组显著增多（P＜0.01）。结论 ES可能通过减少细胞外脂质的沉积,减少内膜和中膜巨噬细胞的数量和胆固醇的含量,增加胶原和平滑肌细胞面积,从而起到逆转斑块的作用。     

Invasion of atheromatous plaques into tunica media causes coronary outward remodeling in WHHLMI rabbits

To clarify the mechanism of coronary outward remodeling, we examined atherosclerotic coronary arteries morphologically using WHHLMI rabbits that develop coronary atherosclerosis spontaneously. Perfusion-fixed coronary segments of WHHLMI rabbits were prepared at 500microm intervals. After immunohistochemical staining and histopathological staining, the areas and lengths of the arterial wall and the lesions were measured. Obvious outward remodeling was observed in coronary sections with greater than 40% cross-sectional narrowing. In coronary sections with greater than 40% cross-sectional narrowing, the tunica media was thick at the shoulder of atheromatous plaque and was thin beneath the atheromatous plaques. Macrophages infiltrated those attenuated tunica media expressed matrix metalloproteinases and oxidized LDL was accumulated in those areas. In those areas, collagen fibers and the internal elastic lamina had disappeared partly and apoptotic smooth muscle cells were observed. Proliferation of smooth muscle cells was observed at the attenuated tunica media and adjacent adventitia. The present results suggest that invasion of atheromatous plaques into the tunica media causes coronary outward remodeling.