动脉粥样硬化易损斑块动物模型的建立

动脉粥样硬化进展、易损斑块破裂导致主要不良心血管事件发生。易损斑块形成机制和干预措施的研究一直备受瞩目。建立与人体斑块相似的进展性斑块是对易损斑块进行研究的基础及热点。目前,研究者已在多种动物体内建立了多种易损斑块模型。本文对目前建立的易损斑块动物模型进行综述与评价,为完善易损斑块模型的建立提供新思路。     

一种纯系小鼠动脉粥样硬化病理模型的建立

实验选用Ｃ５７ＢＬ／６Ｊ纯系小鼠，饲喂含２％胆固醇饮食１６周后，血清脂质（包括总胆固醇、游离胆固醇和甘油三酯）水平升高，血清总胆固醇为３．６９±０．７８ｇ／Ｌ，与人类高脂血症接近；油红Ｏ方法染色后在光镜、激光扫描共聚焦显微镜下观察，形态学结果显示实验组小鼠在主动脉窦瓣膜、冠状动脉等部位均形成典型的含有大量泡沫细胞的动脉粥样硬化斑块，Ｒｏｂｅｒｔｓ＆Ｔｈｏｍｐｓｏｎ评分达到８．０±１．２。这表明成功地建立了一种实验性动脉粥样硬化纯系小鼠整体动物模型。     

动脉粥样硬化斑块的磁共振成像进展(一)——动物模型建立

<正>当前,对于动脉粥样硬化(atherosclerosis,As)的研究是医学心血管领域的热点之一,众多的分子生物学家、临床和影像科医生不懈地对As的分子生物学机制、发展、诊断和治疗等多方面进行深入的研究。因此,建立完善的As动物模型,是基础研究获得突破的重要保障。一个世纪以来,国内外学者先后在鼠、家兔、禽类、猪、食肉类和非人灵长类动物等建立As模型,并进一步的研究。在此基础上,随着多种影像技术的成熟和完善,对As模型的影像学检查,特别是磁共振成像检查(MRI)已经成为斑块成份分析,易损斑块定性     

巨噬细胞与动脉粥样硬化斑块稳定性

在动态粥样硬化病变发展过程中,斑块表面破裂并发血栓形成是极常见的。斑块破裂的危险性取决于斑块的组成成分,往往是巨噬细胞丰富、纤维帽薄、脂质池大的斑块容易破裂。血液中的单核细胞与病变好发区内皮表现粘附分子结合在趋化因子作用下,迁入内膜,然后转化为巨噬细胞,进而经特异受体介导的胞吞作用蓄积脂质,转变成泡沫细胞,形成动脉粥样硬化的早期病变,即脂纹。此时的巨噬细胞不仅形态上变为泡沫细胞,而且新增许多功能,     

一种快速建立大鼠动脉粥样硬化模型的实验方法

目的：建立一种快速制备大鼠动脉粥样硬化模型的实验方法。方法：用大剂量VD3及高脂饲料喂大鼠24d后,测量清甘油三酯、胆固醇含量,制作动脉切片进行形态学观察。结果：模型大鼠血清胆固醇及甘油三酯水平显著升高,动脉内膜细胞增生出现斑块状突出,中膜可见明显的钙化、平滑肌细胞增生及泡沫样细胞,相应的对照组未出现类似变化。结论：用高脂饲料及大剂量VD3可快速诱发大鼠动脉粥样硬化。     

免疫细胞与动脉粥样硬化斑块研究进展

动脉粥样硬化性疾病是导致人类死亡和致残的主要原因之一,动脉粥样硬化易损斑块破裂导致血栓形成是多种急性心脑血管疾病发生的共同病理基础。有关其发病确切机制众说纷纭,本文对目前研究热门的免疫学说的最新研究进展进行综述,探讨免疫在动脉粥样硬化发生发展过程中的作用。     

鼠类动脉粥样硬化模型的制备

动脉粥样硬化（atheroscIerosis,As）是心血管疾病的主要病理基础,有关As斑块的形成机制、发展进程、斑块特性及斑块治疗方面的各类研究一直都是医学领域的热点。因此,建立一种经济、快捷且有效的As动物模型对于As的研究提供了重要保障。在国内外关于As的研究中,鼠类、家兔及猪是目前较为常用的As动物模型。而其中鼠类由于其具有繁殖快、体型小、基因容易获得、易喂养等诸多优势,更是成为医学领域最常应用的一类实验动物,其应用历史已逾百年。本文就目前常用的鼠类As模型的不同制备方法及各常用鼠类As模型特点进行综述。     

动脉粥样硬化性初期斑块的逆转原理

动脉粥样硬化是心肌梗死和脑梗死的主要病因，其发生机理尚未完全阐明，普遍认为，各种诱发因素使来源于血液和坏死细胞的脂质被大中动脉中膜的平滑肌截留在内中膜之间并在此聚积，当这些脂质含量超过局部细胞的消化能力时，诱发动脉壁损伤和慢性炎症，导致脂质条纹、纤维斑块和复合病变等病理变化，造成血管狭窄、器官缺血坏死，并可能由于斑块破例，引起栓塞。     

不同方法建立动脉粥样硬化大鼠模型的比较

目的:比较3种不同方法建立的动物模型,探索建立造型简便且重复性好的大鼠动脉粥样硬化模型。方法健康雄性SD大鼠（体质量150～170g）24只,按3种方法建立模型:①高脂造模组,高脂饲料9周;②维生素D3造模组,维生素D340万单位灌胃3d,标准饲料9周;③高脂维生素D3造模组,维生素D320万单位灌胃3d,高脂饲料9周。采用HE染色鉴定各组的动脉粥样硬化病变形成情况。结果:光镜下高脂组血管各层结构基本正常;维生素D3造模组出现典型动脉粥样病变的斑块结构;高脂维生素D3造模组血管壁钙化和平滑肌细胞增生,程度较维生素D3组减轻,未出现典型斑块结构。结论:40万单位维生素D3的造模方法能在较短时间内建立典型成熟的动脉粥样硬化斑块模型。     

动脉粥样硬化不稳定斑块的研究现状

随不稳定斑块发展而继发的血栓形成是导致急性冠状动脉综合征的重要原因。在内外因素的共同作用下,不稳定斑块可能发生破裂、糜烂以及钙化等现象。斑块中存在许多直接和间接的致血栓形成的物质,它们同血液一起促进了血栓的产生。人们已经建立多种自发或诱发的不稳定斑块的动物模型。针对各种不同的影响斑块稳定性的因素,人们正从不同角度寻找能有效的稳定斑块的治疗方法。     

Reduced plaque formation induced by rosiglitazone in an STZ-diabetes mouse model of atherosclerosis is associated with downregulation of adhesion molecules

Adhesion molecules have been implicated in the development and progression of cardiovascular disease, which is highly prevalent in people with diabetes. Adhesion molecules can mediate adhesion of leukocytes to the endothelium. Furthermore, P-selectin expressed on platelets is able to mediate the adhesion of leukocytes to platelets. In this study, we examine the in-vivo and in-vitro effects of rosiglitazone with particular emphasis on three important adhesion molecules (VCAM-1, ICAM-1 and P-selectin). In the aorta of STZ-diabetic apolipoprotein E-deficient (apoE KO) mice, rosiglitazone significantly reduced both total and arch plaque area. The mechanism for this appeared to be reduced macrophage infiltration into the atherosclerotic plaque which was also associated with reduced mRNA levels for VCAM-1, ICAM-1, MCP-1 and P-selectin in the aorta. In-vitro studies revealed reduced cell adhesion of monocytic cells (THP-1) to fibrinogen and endothelial cells (HUVEC) after incubation with rosiglitazone. Furthermore, the reduction in leukocyte adhesion also correlated with significant reductions in mRNA levels for VCAM-1, ICAM-1 and P-selectin indicating that reduced macrophage infiltration in atherosclerotic plaques may occur as a result of a direct effect of rosiglitazone on adhesion molecules in both monocytes and endothelial cells. Thus, we have shown that rosiglitazone appears to have direct anti-atherosclerotic effects in an animal model of diabetes-associated atherosclerosis which are at least partly due to effects on VCAM-1, ICAM-1, MCP-1 and P-selectin expression which leads to decreased leukocyte adhesion and macrophage infiltration.     

Future non-invasive imaging to detect vascular plaque instability and subclinical non-obstructive atherosclerosis

Atherosclerosis underlies the major causes of death in the Western World. Our main goal is to detect early changes of atherosclerosis and to identify subjects at highest cardiovascular risk that may aid in the development of prevention approaches and better management that will decrease cardiovascular morbidity and mortality. The new methods that are of interest include the advanced vascular ultrasound methods, the infra red and near infra red imaging techniques, the EndoPat device that reflects peripheral arterial tone, the electron beam computed tomography, the magnetic resonance imaging, and the molecular imaging techniques. In this review we will focus on the future of advanced imaging techniques that are being developed to detect early (pre-clinical) development of atherosclerosis.     

Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis

Background

Detection of inflamed atherosclerotic plaques is of crucial importance. The carotid artery cuff-model in ApoE^−/− mice results in shear-stress induced atherosclerosis with inflamed plaques upstream (US) and ‘stable’ plaques downstream (DS) of the cuff. We evaluated the potential of F-18-FDG PET/CT to differentiate these plaque phenotypes.

Methods

A predefined cuff was implanted round the left (n = 23) or right (n = 12) common carotid artery (CCA) of 35 ApoE^−/− mice on a cholesterol-rich diet. Small animal F-18-FDG PET/CT was performed after 4, 6 and 8 weeks. F-18-FDG uptake was quantified US and DS of the cuff and on the contralateral CCA. Subsequently, regional F-18-FDG uptake was normalized by the contralateral CCA uptake to obtain plaque-to-background (P/B)-ratios. Thereafter, CCA were explanted and investigated by immunohistology.

Results

P/B-ratio in the US-plaques increased from 1.22 ± 0.23 at 4 weeks over 1.23 ± 0.32 at 6 weeks to 1.37 ± 0.56 (p = ns) at 8 weeks after cuff implantation (left and right side of cuff implantation considered together). Uptake in the DS-plaques remained stable (1.14 ± 0.23, 1.10 ± 0.26 and 1.11 ± 0.25; p = ns). Uptake in the US-plaques was significantly higher than in the DS-plaques (all p < 0.05). P/B-ratios correlated with plaque size, degree of stenosis and macrophage density in the plaques. Moreover, there was a correlation between plaque size and macrophage density in the plaque.

Conclusions

F-18-FDG-PET/CT distinguishes atherosclerotic plaques with an inflamed from those with a ‘stable’ phenotype in a mouse model of shear-stress induced atherosclerosis in vivo.     

冠状动脉血栓形成的病理生理学——斑块破裂和斑块糜烂的作用

本文综述了冠状动脉粥样硬化血栓形成的病理生理学 ,斑块破裂和斑块糜烂在冠状动脉血栓形成中的作用 ,斑块破裂的机制和稳定斑块的治疗原则     

Virtual histology: a window to the heart of atherosclerosis

Intravascular ultrasound has done much to improve our understanding of atherosclerosis and the impact of percutaneous intervention on the coronary artery. However, subjectivity in interpreting the acoustic reflection of the ultrasound signal has spawned the development of other progressive technologies. Virtual histology intravascular ultrasound (VHIVUS) utilises the ultrasound backscatter signal in order to colour code plaque into four pre-specified subtypes based on their histological composition. We review the background behind traditional grey scale intravascular ultrasound (IVUS) and examine the current evidence for VHIVUS and its potential for use in clinical interventional practice.     

冠状动脉粥样硬化斑块消退的研究进展

<正>随着我国人民生活水平的提高,居民的饮食和生活习惯发生了变化,再加上我国进入老龄化社会,导致冠心病的发病率逐年升高,严重威胁着人们生命健康。近年来,在动脉粥样硬化进展和消退方面国内外研究得到了更多的证据。对动脉粥样硬化过程中的病理生理有了更进一步的认识,并制定了许多可行的治疗策略。这些进展使我们可以考虑把斑块消退作为一个现实的治疗目标。因此,我们将围绕动脉粥样硬化斑块消退这一主题,讨论其现有的治疗证据、抑制因素等,为今后的临床和科研工作提供一些有价值的参考。     

颈动脉不稳定斑块的血清生物标志物

颈动脉粥样硬化尤其是颈动脉不稳定斑块与卒中关系密切.血清生物标志物对于筛查高危颈动脉斑块具有独特的价值.文章对与颈动脉不稳定斑块相关的血清生物标志物进行了综述.     

动脉粥样硬化对大鼠心肌钙敏感受体表达和细胞凋亡的影响

目的 观察高脂血症和动脉粥样硬化对大鼠心肌钙敏感受体(CaSR)表达和细胞凋亡的影响.方法 采用腹腔注射维生素(Vit)D3(6×105U/kg)+高脂饮食6周的方法,建立大鼠高脂血症和动脉粥样硬化模型.Wistar大鼠随机分为正常对照组(n=12)和动脉粥样硬化组(n=12).采用RT-PCR和Western blot分别观察CaSR、Bax、Bcl-2、easpase-3的mRNA和蛋白表达.TUNEL染色观察心肌细胞凋亡情况.光镜观察腹主动脉和心肌形态学变化.电镜观察心脏超微结构变化.紫外分光法检测乳酸脱氢酶、肌酸激酶、超氧化物岐化酶的活性和丙二醛的含量,电化学免疫发光法检测肌钙蛋白水平.结果 动脉粥样硬化组乳酸脱氢酶和肌酸激酶活性、丙二醛含量和肌钙蛋白水平、细胞凋亡指数以及CaSR、Bax和caspase-3的表达均高于对照组,而超氧化物岐化酶活性则低于对照组,Bcl-2表达低于对照组,心肌细胞超微结构损伤严重.结论 高脂血症和动脉粥样硬化可引起大鼠心肌CaSR的表达增加和细胞凋亡,其机制与心肌缺血所致的氧化应激有关.