β-Nicotinamide Mononucleotide Alleviates Sepsis-associated Acute Kidney Injury by Activating NAD+/SIRT3 Signaling.

Acute kidney injury (AKI) following sepsis is a life-threatening condition that portends higher mortality. β-Nicotinamide mononucleotide (β-NMN), a crucial nicotinamide adenine dinucleotide (NAD+) precursor, exhibits the potential to against sepsis. We aimed to elucidate the effect of β-NMN on septic AKI. A cecal ligation and perforation (CLP)-induced sepsis-associated AKI mice model and a lipopolysaccharide (LPS)-triggered HK-2 cell model were established. Renal histopathology in mice with septic AKI without or with β-NMN treatment was detected using H&E staining. The contents of serum creatinine (Scr), blood urea nitrogen (BUN) and renal NAD+ were assessed with kits. Inflammation was evaluated by detecting the concentrations of TNF-α, IL-1β and IL-6 using ELISA kits. Besides, TUNEL assay was used to examine apoptosis and apoptosis-associated proteins was measured using immunoblotting. Additionally, expression of genes in sirtuins (SIRTs) family in renal tissues was tested using RT-qPCR. HK-2 cell viability was detected using CCK-8 assy. Finally, SIRT3 was silenced to carry out the rescue experiments. As a result, NAD+ level was decreased in kidney tissues of mice with sepsis-associated AKI and HK-2 cells treated with LPS. β-NMN treatment increased NAD+ level and alleviated the inflammation and apoptosis in renal tissues. It could be observed that SIRT3 expression was notably downregulated in vivo and in vitro, which was upregulated by β-NMN supplementation. Further, interfering with SIRT3 expression mitigated the protective effects of β-NMN on the inflammation and apoptosis of HK-2 cells under LPS conditions. In summary, β-NMN alleviates sepsis-associated AKI by activating NAD+/SIRT3 signaling. Our findings provide evidence of β-NMN supplementation on improvement of sepsis-associated AKI.