Intervention effect and mechanism of caudal vein injection of astragaloside Ⅳ on renal ischemia-reper-fusion injury in rats
Objective To observe the intervention effect of caudal vein injection of astragaloside Ⅳ on renal isch-emia-reperfusion injury in rats,and to explore the related mechanism based on the regulation of PI3K/AKT signaling path-way and autophagy.Methods Sixty healthy male SD rats were randomly divided into the astragaloside Ⅳ group,wort-mannin group,model group,and control group,respectively.Ischemia-reperfusion injury models were made in the as-tragaloside Ⅳ group,wortmannin group and model group,while in the control group,we only dissociated the renal pedicle of both kidneys and underwent right nephrectomy without other treatment.Rats in the astragaloside Ⅳ group were injected with astragaloside Ⅳ 10 mg/kg at 5 min before reperfusion,while rats in the wortmannin group were injected with astraga-loside Ⅳ 10 mg/kg and wortmannin 0.6 mg/kg(PI3K specific inhibitor)at 5 min and 10 min before reperfusion,respec-tively.Rats in the control group and the model group were injected with equal volume of normal saline at the same time.Serum creatinine(Cr)and urea nitrogen(BUN)were detected at 24 h after reperfusion.Renal tissue was stained with HE to observe the pathological changes.We observed the apoptosis of renal cells and calculated the apoptosis index,and de-tected microtubule-associated protein light chain 3-Ⅱ(LC3),Beclin-1 and phosphorylated AKT(p-AKT)in renal tis-sues.Results The levels of serum Cr and BUN in the astragaloside Ⅳ group,wortmannin group and model group were higher than those in the control group,while the levels of serum Cr and BUN in the model group,wortmannin group and as-tragaloside Ⅳ group decreased in turn(all P<0.05).Compared with the model group,the pathological damage of renal tis-sue in the astragaloside Ⅳ group and wortmannin group was reduced,especially in the astragaloside Ⅳ group.Apoptosis index and the expression levels of LC3-Ⅱ,Beclin-1 and p-AKT protein in the renal tissues of the astragaloside Ⅳ group,wortmannin group and model group were higher than those in the control group,but the apoptosis index and the expression levels of LC3-Ⅱ and Beclin-1 protein in the model group,wortmannin group and astragaloside Ⅳ group decreased in turn,and the expression of p-AKT protein in wortmannin group was lower than that in astragaloside Ⅳ group(all P<0.05).Conclusion Astragaloside Ⅳ intervention can alleviate renal ischemia-reperfusion injury in rats,and its mechanism may be related to regulating PI3K/AKT pathway and inhibiting autophagy.
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