基于微流控的炎症应激型IDILI评价模型的构建
首发时间:2022-11-11
摘要:特异质型药致肝损伤(Idiosyncratic Drug-Induced Liver Injury,IDILI)是药物上市后在临床发生肝毒性的主要原因,其发生率不高,但可能导致肝衰竭等严重肝病,且发生机制尚未明确。炎症应激机理是特异质型药致肝损伤的重要假说之一,目前主要依赖于低剂量LPS动物模型进行表征,但动物模型的参数常随着药物而改变,而且不能对肝区炎症进行及时检测。本文利用微流控技术的灵活性,构建了包含HepG2、U937巨噬、LX-2、EA.hy926细胞的层叠式肝芯片以及炎症模型,并评价了已知炎症应激型肝损伤药物曲格列酮。该芯片操作友好,通量高,可平行比较不同条件下芯片中的细胞表观活力,有助于我们更好地理解炎症应激型药致肝损伤。
关键词: 微流控芯片 炎症应激 特异质型药致肝损伤 脂多糖 曲格列酮
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Construction of inflammatory stress IDILI model based on microfluidics
Abstract:Idiosyncratic Drug-Induced Liver Injury (IDILI) is the main pathogeny of clinical hepatotoxicity in post-marketing surveillance. It has low incidence, but may cause serious consequence such as liver failure. The mechanism has not yet been clarified. Inflammatory stress is one of the important hypotheses of idiosyncratic drug-induced liver injury. At present, it mainly relies on low-dose LPS animal models for characterization. However, due to different drug, the parameters of animal models often change, and hepatic inflammation situation can not be detected promptly. In this paper, based on flexible microfluidic technology, a laminated liver chip containing HepG2, U937 macrophages, LX-2, EA.hy926 cells and an inflammation model were constructed, and troglitazone, the known IDILI drug, was evaluated. This chip is a powerful tool with friendly operation and high throughput, and can be used to parallelly evaluate apparent activity of cells under different conditions. With the chip, we can get better understanding of inflammatory stress drug-induced liver injury.
Keywords: Microfluidic Chip Inflammatory stress Idiosyncratic drug-induced liver injury Lipopolysaccharide Troglitazone
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