Ligustrazine suppresses renal NMDAR1 and caspase-3 expressions in a mouse model of sepsis-associated acute kidney injury.

ABSTRACT

Sepsis-associated acute kidney injury (AKI) is a life threatening condition with high morbidity and mortality. The pathogenesis of AKI is associated with apoptosis. In this study, we investigated the effects of ligustrazine (LGZ) on experimental sepsis-associated AKI in mice. Sepsis-associated AKI was induced in a mice model using cecal ligation and puncture (CLP) method. Mice were administered LGZ (10, 30, and 60 mg/kg) via tail vein injection 0.5 h before CLP surgery. Mice survival was evaluated. Renal water content was detected. Urine samples were collected for ELISA of Kim1. Kidneys were collected for nucleic acid analysis and histological examination. Pathological assessment was used to determine the effect of LGZ on sepsis-associated AKI. Caspase-3 expression in kidney was assessed by immunohistochemistry. Renal NMDAR1 level was also determined. Treatment of LGZ improved mice survival rate; the effect was significant when administered at a high LGZ dose (60 mg/kg). Renal water content of mice undergoing CLP was significantly reduced by LGZ treatment. Both middle-dose and high-dose LGZ treatments reduced urine Kim1 level in sepsis-associated AKI mice. The severity of AKI in septic mice was reduced by middle-dose and high-dose LGZ administration. Immunohistochemical analysis revealed decreased caspase-3 and NMDAR1 levels in the kidney following middle-dose and high-dose LGZ treatments. RT-PCR assay showed a significant reduction in NMDAR1 mRNA expression in the kidney of middle-dose and high-dose LGZ-treated mice. LGZ exhibited protective effects against sepsis-associated AKI in mice, possibly via downregulation of renal NMDAR1 expression and its anti-apoptotic action by inhibiting caspase-3.