Effect of ticagrelor on acute kidney injury in septic rats and its underlying mechanism.

Abstract

The aim of the present study was to determine whether the effects and underlying mechanisms of ticagrelor in a rat model of sepsis-induced acute kidney injury (AKI) were mediated via the CD62P pathway. A total of 15 rats were randomly assigned to the following groups: Normal, sham, cecal ligation and puncture (CLP), CLP + clinical dose of ticagrelor (CCD) and CLP + loading dose of ticagrelor (CLD). Ticagrelor was administered 12 h before modeling, immediately after modeling, and 12 h after modeling at a dose of 8.6 and 46.42 mg/kg in the CCD and CLD groups, respectively. Rats in the normal, sham and CLP groups were treated with the same volume of distilled water. Serum creatinine (SCr), CD62P and interleukin-1β (IL-1β) levels, myeloperoxidase (MPO) activity in the renal tissue and the apoptosis rate of renal cells were increased in the CLP group, compared with in the normal and sham groups (P<0.05). In addition, ticagrelor treatment reduced SCr, CD62P and IL-1β expression levels, renal tissue MPO activity and renal cell apoptosis in rats with sepsis-induced AKI (P<0.05). CD62P expression was closely associated with the occurrence of sepsis-induced AKI. The mechanism of ticagrelor-mediated reductions in inflammation, renal neutrophil infiltration and renal cell apoptosis is possibly associated with reductions in CD62P expression.