Abstract: Objective To explore the inhibitory effect of astragaloside IV (AS-IV) on podocyte injury induced by puromycin aminonucleoside (PAN) and its underlying mechanism.Methods A PAN-induced podocyte injury model was established to evaluate the effect of AS-IV on podocyte apoptosis. Based on different treatment, The MPC5 podocytes were randomly divided into 4 groups:control group, PAN group (50 μg/mL PAN,24h), AS-IV group (5 μg/mL, 15 μg/mL, 30 μg/mL AS-IV, 24 h) and AS-IV+PAN group (pretreated with AS-IV for 30 min, then treated with PAN for 24 h). CCK-8 was used to detect growth activity of podocytes, Annexin V/PI double staining method to detect podocyte apoptosis, immunofluorescence assay to detect the marker protein in podocytes, Western blot to detect the protein expression levels of Caspase-3, cleaved Caspase-3 and VEGFR2/GIV pathway.Results Compared with the control group, in the PAN group the podocyte apoptotic rate was significantly increased (P<0.05), the expression of nephrin and podocin was decreased notably(P<0.05), and the levels of cleaved caspase-3, p-VEGFR2 and p-GIV were up-regulated significantly(P<0.05). Compared with the PAN group, the podocyte apoptotic rate and protein levels of cleaved caspase-3 was dramatically declined in the AS-IV+PAN group(P<0.05), accompanied with obvious increase of nephrin and podocin levels(P<0.05), significant decrease of cleaved caspase-3, and further upregulation of p-VEGFR, p-GIV and p-AKT (P<0.05).Conclusions Astragaloside IV attenuates puromycin aminonucleoside induced podocyte injury and it may be mediated by the VEGFR2/GIV signaling pathway.