摘要
Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogen-esis.However,current cell-based models lack a comprehensive understanding of crosstalk between mac-rophages and cardiomyocytes,hindering the discovery of effective therapeutic interventions.Here,a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes,allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury.Through metabolic profiling and bioinformatic enrich-ment analysis,the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflam-matory and oxidative stress-associated metabolic pathways,closely resembling metabolic profiles of myocardial infarction in both humans and rodents.Furthermore,an integrative screening strategy has been established to screen bioactive natural products precisely,identifying ginsenoside Rb 1 and protoca-techualdehyde as promising cardioprotective candidates in vitro and in vivo.Taken together,the micro-fluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.
基金
supported by the National Natural Science Foundation of China(U23A20514,82174086,82173949, 82100295)
the National Key Research and Development Project(2023YFC3505000,China)
the Key Research and Development Project of Shandong Province(2021CXGC010507,China)
the Beijing Natural Science Foundation(7222273,China).
