Ulinastatin-Gold Nanoparticles Reduce Sepsis-Induced Cardiomyocyte Apoptosis Through NF-κB Pathway Inactivation

Nanodrug delivery systems have recently become widely studied and applied in the medical field, and nanomaterials have greatly improved drugs' efficacy. Ulinastatin has been confirmed to inhibit myocardial damage caused by sepsis. However, the effect and mechanism of ulinastatin-gold nanoparticles (UTI-GN) on sepsis-induced cardiomyocyte apoptosis are unknown. Here we explore the effect and mechanism of UTI-GN on sepsis-induced cardiomyocyte apoptosis. Lipopolysaccharide (LPS) was used to stimulate rat cardiomyocytes to construct an in vitro sepsis model. Enzymelinked immunosorbent assay detected cellular inflammatory factors NF-alpha, IL-1 beta, and IL-6. Western blots measured iNOS and COX-2 expression. Based on LPS-treated cells, different concentrations of UTI-GN were applied to cardiomyocytes. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) experiments and flow cytometry measured cell viability and apoptosis, respectively. Western blots evaluated apoptotic protein expression of NF-kappa B, iNOS, and COX-2. The NF-kappa B pathway inhibitor BAY11-7082 was further used to explore whether UTI-GN played a regulatory role through the NF-kappa B pathway. LPS promotes NF-alpha, IL-1 beta, and IL-6 production and iNOS and COX-2 expression in cardiomyocytes. The results of the MTT experiment showed that UTI-GN has little toxicity to cardiomyocytes. The flow cytometry and western blot experiments showed that UTI-GN kpromoted cell apoptosis and inhibited NF-kappa B expression. Additionally, the NF-kappa B pathway inhibitor BAY11-7082 counteracts the UTI-GN effect. UTI-GN inhibits sepsis-induced cardiomyocyte apoptosis through NF-kappa B pathway inhibition.