植入小鼠触发剪应力致动脉粥样硬化的颈袖
Summary
本文介绍的收缩袖口的设计，以诱导小鼠左颈总动脉粥样硬化。由于其内腔的圆锥形植入袖口产生良好定义的低，高和振荡剪切引发动脉粥样硬化病变的不同炎症表型的发展压力的地区。
Abstract
它已被广泛接受，血管剪应力的改变引发的内皮细胞的炎性基因表达，从而诱发动脉粥样硬化（1和2审查）。剪切力的作用已被广泛研究，在体外血流动力学1,3,4对体外培养的内皮细胞的影响进行调查，并在较大 的动物和人类1,5,6,7,8的体内。然而，高度重复性的小动物模型，使斑块发展的剪应力的影响进行系统的调查是罕见的。近日，南等9中引入的一个小鼠模型中，结扎颈内动脉的分支创建一个低和振荡流的地区。尽管这种模式导致血管内皮功能障碍和高脂血症小鼠动脉粥样硬化病变的迅速形成，它不能被排除，所观察到的炎症反应是，至少有一部分，因此Øf内皮细胞和/或因结扎血管损伤。
为了避免这种局限性，剪应力修改袖口已经开发基于计算流体动力学，其锥体形内腔被选为低，高和振荡剪切应力定义的区域内常见的颈动脉10。通过应用这个模型中载脂蛋白E（APOE）基因敲除小鼠喂食高胆固醇，西方型饮食，血管病变发展的上游和下游，从袖口。其表型相关， 证实在体内磁共振成像（MRI）12区域流动的动态 11：低和层剪应力的袖口上游原因形成的一个更容易的表型广泛的斑块，而振荡剪切应力下游袖口诱导稳定动脉粥样硬化病变11。在这些地区的高剪切应力和高层流内的袖口，通常没有观察到动脉粥样硬化斑块。
总之，剪应力修改袖口过程是一个可靠的生产ApoE基因缺陷小鼠的表型不同的动脉粥样硬化病变的手术方式。
Protocol
1。准备剪应力修饰符（袖口） 剪应力修饰符 由两个纵向半圆柱与一个锥形腔。半壳是塑料铸造过程中产生的热塑性聚醚。投元素发送出去，同时仍然连接到亚军。因此，使用前不得不削减一半炮弹。每个投包含范围从150微米 – 300微米（下游终端的最低内径）的一半大小不同的炮弹。 袖口准备应在手术显微镜下进行。 保持钝钳袖口半壳，轻轻地削减自投使用锋?…
Discussion
为了尽量减少实验误差，建议用几乎相同的年龄动物具有相同的饮食历史。最近发表的一份调查表明，剪应力调节剂，适用于野生型小鼠可能是一个很好的模式和改变血流动力学13诱导的内皮功能障碍的早期炎症反应的调查。然而，对于动脉粥样硬化斑块的发展转基因高脂血症小鼠模型的查询（如ApoE基因敲除小鼠）。每个小鼠模型的进展和斑块沉积的程度取决于使用饮食类型。在一?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
这项研究是支持的，一部分由德意志研究联合会（DFG）的，项目广州PI 771/1-1; SFB 656“心血管分子成像”，德国明斯特（项目C6，Z2，B3，和PM3）;欧盟NOE“诊断分子成像迪米“（可湿性粉剂11.1和11.2）。这项研究还资助部分由英国心脏基金会，英国。
Materials
| Name | Company | Comments |
| Shear stress modifier (polyetherketone) | Promolding BV http://promolding.nl | The casts are sent out while still connected to the runner. Thus, the single elements have to be cut off before usage. |
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Tags
Carotid CuffShear StressAtherosclerosisInflammatory GenesEndothelial CellsFlow DynamicsSmall Animal ModelsPlaque DevelopmentCarotid Artery LigationEndothelial DysfunctionAtherosclerotic LesionsShear Stress Modifying CuffFluid DynamicsDefined Regions Of Shear StressCommon Carotid ArteryApolipoprotein E (ApoE) Knockout MiceHigh Cholesterol Diet
Cite This Article
Kuhlmann, M. T., Cuhlmann, S., Hoppe, I., Krams, R., Evans, P. C., Strijkers, G. J., Nicolay, K., Hermann, S., Schäfers, M. Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice. J. Vis. Exp. (59), e3308, doi:10.3791/3308 (2012).