动脉粥样硬化兔模型中主动脉瓣硬化的发展:一项免疫组织化学和组织学研究。

Development of aortic valve sclerosis in a rabbit model of atherosclerosis: an immunohistochemical and histological study.

作者信息

Cimini Massimo, Boughner Derek R, Ronald John A, Aldington Lori, Rogers Kem A

机构信息

University of Western Ontario, Department of Anatomy and Cell Biology, Canada.

出版信息

J Heart Valve Dis. 2005 May;14(3):365-75.

DOI:
Abstract

BACKGROUND AND AIM OF THE STUDY

It has been suggested that aortic valve sclerosis (AVS) is an atherosclerotic disease process that can proceed to aortic stenosis. The absence of reports studying an animal model of the early stages of this disease has precluded the development of preventive therapeutic strategies. A cholesterol-fed (0.25% cholesterol in chow) rabbit model of atherosclerosis that is characterized by a moderate level of hypercholesterolemia was studied to determine its efficacy as a model of early AVS. Cellular, structural and morphological changes in the aortic valves of these rabbits were studied.

METHODS

Twenty rabbits were assigned randomly to four experimental groups: Group 1 received normal chow for 40 weeks; group 2 received 0.25% cholesterol-supplemented chow for 20 weeks; group 3 received 0.25% cholesterol-supplemented chow for 40 weeks; and group 4 received 0.25% cholesterol-supplemented chow for 20 weeks followed by normal chow for an additional 20 weeks. The aortas and aortic valves were analyzed using immunohistochemical and histological methods to detect cellular and structural components of the developing lesions.

RESULTS

All rabbits in groups 2, 3 and 4 developed atherosclerotic lesions in their aortas. Aortic valves from these animals demonstrated thickening, lipid deposition, a change in collagen content and organization, a reorganization of elastin, and the presence of both macrophage infiltrate and osteopontin.

CONCLUSION

These findings were consistent with the suggestion of a link between atherosclerosis and AVS. Results were also similar to changes reported in human sclerotic aortic valves, suggesting the suitability of this rabbit model of atherosclerosis as a model for AVS.

摘要

研究背景与目的

有人提出主动脉瓣硬化(AVS)是一种可发展为主动脉狭窄的动脉粥样硬化疾病过程。由于缺乏对该疾病早期阶段动物模型的研究报告,阻碍了预防性治疗策略的开发。我们研究了一种以中度高胆固醇血症为特征的高胆固醇饮食(饲料中含0.25%胆固醇)兔动脉粥样硬化模型,以确定其作为早期AVS模型的有效性。对这些兔子主动脉瓣的细胞、结构和形态变化进行了研究。

方法

将20只兔子随机分为四个实验组:第1组接受正常饲料喂养40周;第2组接受含0.25%胆固醇的饲料喂养20周;第3组接受含0.25%胆固醇的饲料喂养40周;第4组接受含0.25%胆固醇的饲料喂养20周,随后再接受正常饲料喂养20周。使用免疫组织化学和组织学方法分析主动脉和主动脉瓣,以检测病变发展过程中的细胞和结构成分。

结果

第2、3和4组的所有兔子主动脉均出现动脉粥样硬化病变。这些动物的主动脉瓣表现出增厚、脂质沉积、胶原蛋白含量和结构的变化、弹性蛋白的重新组织,以及巨噬细胞浸润和骨桥蛋白的存在。

结论

这些发现与动脉粥样硬化和AVS之间存在联系的观点一致。结果也与人类硬化主动脉瓣中报道的变化相似,表明这种兔动脉粥样硬化模型适合作为AVS模型。

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