Revascularization is an effective therapy for rescuing myocardial tissue after ischemic events. However, the process of reperfusion can lead to more severe cardiomyocyte damage, called myocardial ischemia-reperfusion (I/R) injury (MIRI). We have previously shown that vitexin (VT) (a flavonoid compound derived from natural products) protects against MIRI; however, the exact mechanisms underpinning this effect require further elucidation. This study is aimed at elucidating the protective mechanism of VT in inhibiting ischemic myocardial mitochondrial dysfunction and reducing cardiomyocyte apoptosis by regulating Epac1-Rap1 signaling. Isolated rat hearts were subjected to MIRI in a Langendorff perfusion system, and H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. Our analyses show that during I/R, Epac1 expression was upregulated, left ventricular dysfunction deteriorated, mitochondrial dynamics were disrupted, and both myocardial cells and tissues exhibited apoptosis. Furthermore, administration of 8-CPT (an Epac agonist) exacerbated cardiomyocyte injury and mitochondrial dysfunction. Interestingly, suppressing the function of Epac1 through VT or ESI-09 (an Epac inhibitor) treatment during I/R reduced the myocardial infarct size, cardiomyocyte apoptosis, and reactive oxygen species production; alleviated mitochondrial dysfunction by increasing mitochondrial membrane potential; elevated MFN2 expression; and inhibited Drp1 expression. To our knowledge, our results reveal, for the first time, the mechanisms underlying the protective effect of VT in the myocardium of rats with MIRI. Moreover, we provide a new target and theoretical basis for VT in the treatment of ischemic heart disease.

Untethered biocompatible microswimmers driven by micromotors in fluids can enable innovative technologies in fields such as biology and chemical and biomedical engineering. However, efficiently driving and controlling the movement of microswimmers by light remains a challenge. Herein, a method for fabricating a light‐driven microswimmer with built‐in micromotors and 3D‐printed multiscale features that exhibits high photocatalytic performance is proposed. TiO2‐CaCO3 composite microparticles (TC) are fabricated as highly efficient micromotors that provide high photocatalytic efficiency in bubble generation, while 3D‐printed hydrogels are fabricated as TiO2‐CaCO3/PEGDA (TC/P) microswimmers that provide biocompatibility, large specific surface area, and controllable movement. The results show that TC micromotors produced by physical mixing at a specific concentration exhibit a large specific surface area, reduced agglomeration, increased photocatalytic active sites, and improved photocatalytic stability. TC micromotors are effectively loaded into the porous hydrogel by 3D printing for multiscale fabrication to improve the photocatalytic performance across scales and realize effective and directional driving under violet light excitation. The TC/P microswimmers exhibit stable catalysis and motion in 7 days, at which point the catalysis by TiO2 is already ineffective. With stability, biocompatibility, and biomedical functions, this multiscale fabricated microswimmer exhibits great potential in micromanipulation and targeted therapy.