Shenfu Injection Alleviates Lipopolysaccharide-Induced Septic Acute Kidney Injury by Regulating the Nrf2/NF-κ B Axis

Abstract

This study investigated the protective effect of Shenfu injection (SI) on septic acute kidney injury (AKI) induced by lipopolysaccharide (LPS) and its underlying mechanism. A mouse model of septic AKI was established, and various dosages of SI (2 mL/kg, 4 mL/kg, and 8 mL/kg) were administered as treatment. HE staining and TUNEL assay were conducted for pathological analysis. The content of ATP was detected by the biochemical kit. The mitochondrial membrane potential (MMP) was detected by flow cytometry. Western blotting was used for the detecting expression of apoptosis and inflammation related proteins. To explore the molecular mechanism, septic mice were treated by SI (8 mL/kg) combined with ML385 (30 mg/kg). The number and morphology of mitochondria were observed by the transmission electron microscope (TEM). The increased renal volume, paler renal cortex, and necrotic renal tubules observed in septic AKI mice were significantly alleviated by treatment with either 4 mL/kg or 8 mL/kg of SI. Furthermore, signally declined ATP content and increased MMP value in septic AKI mice were markedly reversed by 8 mL/kg SI. Additionally, the increased IL-6, p-p65, cle-caspase-3, and Bax levels, as well as the decreased Bcl-2 level, observed in septic AKI mice were notably rescued by 8 mL/kg SI. The protective function of SI on pathological changes and mitochondria in septic AKI mice was abolished by ML385. These findings suggested that SI alleviated LPS-induced septic AKI by regulating the Nrf2/NF-κB axis.