Effects of PI3K inhibitor LY294002 on renal function and autophagy in rats with acute kidney injury
Objective To explore the effect of LY294002 on renal function and autophagy in rats with acute kidney injury(AKI).Methods Thirty-six SD rats were divided into control group,sham group,model group and LY294002 preconditioning(I/R+LY294002)group,using the randomized unit group design,with nine rats in each group.LY294002 was injected continuously intraperitoneally(40 μl/d)in the LY294002 preconditioning group,and an equal amount of sterile saline was injected intraperitoneally in the model group,and the intervention time was 14 days.After 14 days,all rats except the control group underwent operation.Only bilateral kidneys and renal hila were exposed in the sham group,while the rat renal ischemia-reperfusion injury(RIRI)model(ischemia for 45 min,reperfusion for 24 h)was further established to simulate AKI in the model group and the LY294002 preconditioning group.After successful modeling,blood and kidneys were collected from each group,the renal injury-related indexes in serum were detected,histopathological changes in kidneys were observed,the expression of PI3K/AKT signaling pathway and autophagy-related proteins were detected.Results The concentrations of serum creatinine(SCr),blood urea nitrogen(BUN)and kidney injury molecule 1(Kim-1)in the model group were higher than those in the control group and sham group,and the differences were statistically significant(P＜0.05).The concentrations of SCr,BUN and Kim-1 in the LY294002 preconditioning group were lower than those in the model group,and the differences were statistically significant(P＜0.05).Histopathological changes in the kidneys of RIRI rats,such as dilatation of tubular obstruction,vasodilatation and congestion,and interstitial oedem were observed to be attenuated in the LY294002 preconditioning group.The relative expression of p-AKT/AKT and p-PI3K/PI3K and the expression of LC3 Ⅱ and Beclin-1 in the model group were higher than those in the control group and sham group,and the differences were statistically significant(P＜0.05).The relative expression of p-AKT/AKT and p-PI3K/PI3K and the expression of LC3 Ⅱ and Beclin-1 in the LY294002 preconditioning group were lower than those in the model group,and the differences were statistically significant(P＜0.05).Conclusion LY294002 could inhibit autophagy to ameliorate the kidney injury by inhibiting the PI3K/AKT signaling pathway,which might provide a new way for the prevention and treatment of AKI.
万方数据
维普
