| Objective:To investigate the protective effect of Acteoside(Act)on diabetic kidney disease(DKD),and to explore its mechanism from the perspective of podocyte apoptosis and AKT/GSK-3β signaling pathway.It provides a new option for finding more effective drugs of treating DKD.Methods:In this study,C57BLKS/J db/db mice were used as DKD animal model,and their homogenous wild-type db/m mice were normal control group.8 weeks after Act administration,the 24-hour urine protein and biochemical indexes of mice in each group were determined by using corresponding kits.HE and PAS staining were used to observe the pathological changes of the mice kidney.TUNEL staining and Western Blot were used to tset the injury and apoptosis of renal podocyte in db/db mice,and the expression of protein kinase B(AKT),glycogen synthase kinase 3β(GSK-3β)and apoptosis-related signaling proteins were detected by Western Blot.Results:(1)With the administration of Act,the albuminuria of db/db mice was reduced from 391μg/24 h to 152μg/24 h.(2)Act treatment reduced the glomerular hypertrophy of db/db mice,and reduced the proliferation of mesangial cells,mesangial matrix deposition,basement membrane thickening,podocytes reduction.(3)The expression of podocin and synaptopodin were decreased in db/db mice,and Act administration significantly upregulated the expression of podocin and synaptopodin,reduced the podocytes injury in db/db mice.(4)Act intervention up-regulated the expression of Bcl-2 in db/db mice,down-regulated the expression of Bax and cleaved caspase-3,and inhibited the occurrence of renal apoptosis in db/db mice.(5)TUNEL staining showed that the apoptotic activity of db/db group was significantly higher than db/m group,and Act treatment inhibitd the apoptotic activity in db/db mice.Conclusion:(1)Act reduced 24-hour proteinuria and had renoprotective effect on db/db mice.(2)Act alleviated the renal podocytes injury and inhibited its apoptosis activity in db/db mice.(3)Act remarkably inhibited the activation of AKT/GSK-3β signaling pathway of db/db mice kidney. |
