Resveratrol protects against sepsis-induced acute kidney injury in mice by inducing Klotho-mediated apoptosis inhibition

Purpose: To investigate the mechanism of resveratrol protection against sepsis-induced acute kidney injury in mice.Methods: A sepsis-induced acute kidney injury model was established in mice by cecal ligation and puncture (CLP). Sixty healthy male ICR mice were randomly divided into the sham operation (sham) group, sepsis-induced acute kidney injury model (CLP) group, CLP + low-dose (20 mg/kg) resveratrol treatment (CLP + ResL) group, CLP + high-dose (40 mg/kg) resveratrol treatment (CLP + ResH) group and CLP + Klotho (0.01 mg/kg) treatment (CLP + Klotho) group. All mice were administered treatment on the day after surgery and once every 24 h for 3 days. Various serum biochemical parameters and protein expressions were evaluated.Results: After CLP, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) increased and the pathology was exacerbated. The protein and mRNA expression levels of Klotho and Bcl-2 decreased, while those of Bax and Caspase-3 increased (p < 0.05). After resveratrol and Klotho protein intervention, Scr and BUN levels recovered, and pathological changes were alleviated. The protein and mRNA expression levels of Klotho and Bcl-2 increased, while those of Bax and Caspase-3 decreased. The conditions of the mice in CLP + ResH group and the CLP + Klotho group improved more significantly than those of the mice in the CLP + ResL group (p < 0.05).Conclusion: Resveratrol upregulates the expression of endogenous Klotho to exert its antiapoptotic effects, which can protect the kidneys of mice against sepsis-induced acute kidney injury. Thus, the compound has potentials for development for protection against acute kidney injury.