University Hospital Basel, Nanomedicine Group, Clinic for Intensive Care, Petersgraben 4, CH-4031 Basel, Switzerland.
J Biomed Opt. 2012 Jul;17(7):076006. doi: 10.1117/1.JBO.17.7.076006.
Existing mouse artery ex vivo perfusion models have utilized arteries such as carotid, uterine, and mesenteric arteries, but not the aorta. However, the aorta is the principal vessel analyzed for atherosclerosis studies in vivo. We have devised a mouse aorta ex vivo perfusion model that can bridge this gap. Aortas from apoE((-/-)) mice are embedded in a transparent, gas-permeable, and elastic polymer matrix [polydimethylsiloxane (PDMS)] and artificially perfused with cell culture medium under cell culture conditions. After 24 h of artificial ex vivo perfusion, no evidence of cellular apoptosis is detected. Utilizing a standard confocal microscope, it is possible to image specific receptor targeting of cells in atherosclerotic plaques during 24 h. Imaging motion artifacts are minimal due to the polymer matrix embedding. Re-embedding of the aorta enables tissue sectioning and immuno-histochemical analysis. The ex vivo data are validated by comparison with in vivo experiments. This model can save animal lives via production of multiple endpoints in a single experiment, is easy to apply, and enables straightforward comparability with pre-existing atherosclerosis in vivo data. It is suited to investigate atherosclerotic disease in particular and vascular biology in general.
现有的鼠离体动脉灌注模型已经使用了颈动脉、子宫和肠系膜等动脉，但不包括主动脉。然而，主动脉是用于体内动脉粥样硬化研究的主要血管。我们设计了一种鼠离体主动脉灌注模型，可以弥补这一空白。apoE(-/-) 小鼠的主动脉被嵌入透明、透气、弹性聚合物基质[聚二甲基硅氧烷 (PDMS)]中，并在细胞培养条件下用人造培养基进行人工灌注。经过 24 小时的人工离体灌注，没有检测到细胞凋亡的证据。利用标准共聚焦显微镜，可以在 24 小时内对动脉粥样硬化斑块中细胞的特定受体靶向进行成像。由于聚合物基质的嵌入，成像运动伪影最小。主动脉的重新嵌入使得组织切片和免疫组织化学分析成为可能。通过与体内实验进行比较，验证了离体数据的可靠性。该模型可以通过在单次实验中产生多个终点来挽救动物生命，易于应用，并可以与现有的体内动脉粥样硬化数据进行直接比较。它适用于研究动脉粥样硬化疾病特别是血管生物学。
