微流体 perfusable 病理血管为动脉样硬化 药物查 药物查
Jing Liu1,2, Mulan Zhu1,2, Na Bai1,2
1The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong 523059, China.
Research (Washington, D.C.)
|September 22, 2025
概括
一个新的3D可 perfusable 动脉样硬化器-on-a-chip (3D-PAVoC) 平台通过包括血流来更好地模拟动脉样硬化 (AS). 这种先进的模型准确地预测了抗AS药物的疗效,弥合了实验室测试和动物研究之间的差距.
科学领域:
- 生物医学工程 生物医学工程
- 心血管研究研究心血管研究
- 药物发现 药物发现 药物发现
背景情况:
- 目前的体外动脉样硬化模型由于缺乏血液流动而缺乏生理相关性.
- 这种局限性阻碍了在动脉样硬化 (AS) 发展过程中内皮损伤和药物运输动态的准确复制.
研究的目的:
- 开发一个3D可 perfusable 动脉样血管在芯片上 (3D-PAVoC) 平台,它结合了血液动力学力.
- 建立一个更生理相关的体外模型来研究AS和评估抗动脉样硬化药物疗效.
主要方法:
- 设计了一种能够流动的动脉结构,整合了内皮细胞和光滑肌肉细胞.
- 将构造暴露在炎症和超脂血性刺激中,以诱导易患AS的疾病.
- 使用拉巴胺素 (RAP) 评估药物反应和在ApoE敲击小鼠中验证的结果.
主要成果:
- 与静态模型相比,3D-PAVoC平台显示了流量依赖的内皮反应和更明显的AS病理.
- 在3D-PAVoC中进行的药物有效性测试显示了较高的RAP半最大抑制度,与体内结果更好地相关.
- 在ApoE-/-小鼠体内验证证,通过确定RAP剂量,证实了AS进展的部分缓解.
结论:
- 3D-PAVoC平台通过结合关键的血液动力学因素,为动脉样硬化研究提供了卓越的体外模型.
- 该模型增强了对抗动脉样硬化药物疗效的预测,改善了体外发现的转化为体外结果.
- 该平台提供了在真实的血管和病理条件下对药物机制的宝贵见解.
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