Role of the early intervention of Caspase-3 inhibitor in acute kidney injury induced by sepsis

Objective To explore the role of the early intervention of Caspase-3 inhibitor (CI) in acute kidney injury (AKI) induced by sepsis.Methods Seventy-two healthy male C57BL/6 mice were assigned into three groups (n =24 each):sham group,cecal ligation and puncture (CLP) group and CI group.Thirty min afterCLP,Ac-DEVD-CHO (4 μg/g) was injected subcutaneously in CI group.The levels of blood urea nitrogen (BUN) and creatinine (Cr) were determined,and the renal cell apoptosis rate was measured by flow cytometry at 6,12 and 24 h after operation and the expression levels of renal Caspase-3,B lymphocytes/leukemia-2 (bcl-2) and bax proteins were detected by using immunohistochemistry at 24 h after operation.Pathological changes in renal tissues were observed under a light microscope.Results As compared with sham group,the concentrations of serum Cr at 6 h and BUN at 6 h and 12 h after operation were significantly increased (P ＜ 0.05),kidney tissue pathological damage score and renal cell apoptosis rate at all time points were significantly elevated ( P ＜ 0.05 ),and the renal expression levels of Caspase-3,bcl-2 and Bax proteins were significantly increased at 24 h after operation ( P ＜ 0.05 ) in CLP group.As compared with CLP group,the concentrations of serum Cr and BUN were decreased significantly at 6 h after operation [ serum Cr:(83.82 ± 10.15 ) μmol/L vs.( 123.05 ± 33.48) μmol/L; BUN:( 10.15 ±4.34) mmol/L vs.( 14.02 ± 3.51 ) mmol/L,all P ＜ 0.05 ] ; mouse kidney tissue pathological damage score and renal cell apoptosis rate at all time points were significantly decreased [ kidney tissue pathological damage score at 6 h:(0.88 ± 0.64) points vs.(2.17 ± 0.75 ) points,at 12 h:( 0.63 ±0.74) points vs.( 1.83 ±0.98) points,at 24 h:(1.83 ±0.98) points vs.(1.33 ±0.52) points; renal cell apoptosis rate at 6 h:(13.28 ±0.91)％ vs.(18.27 ±1.40)％,at 12 h:(9.71±0.91)％ vs.(15.86 ±3.51)％,at 24h:(8.45 ±0.55)％ vs.(12.48 ±2.14)％,allP＜0.05]; the expression levels of Caspase-3 and Bax in kidney tissue were down-regulated significantly ( P ＜ 0.05 ),but bcl-2 expression was up-regulated significantly (P ＜ 0.05 ) in CI group.Conclusion The selective Caspase-3 inhibitor has renal protective effect on sepsis-related AKI by the inhibition of renal cell apoptosis. Key words: Sepsis; Acute kidney injury; Caspase-3; Apoptosis