Effect of astragaloside IV combined with glucocorticoids on puromycin aminonucleoside-induced rat nephropathy model and the associated mechanism / 中华肾脏病杂志

ABSTRACT

Objective:To investigate the effect and mechanism of astragaloside IV (AS-IV) combined with glucocorticoids in the treatment of puromycin aminonucleoside (PAN) rat nephropathy model.Methods:Forty specific pathogen-free healthy male Wistar rats (150-180 g) were randomly divided into 5 groups control group, PAN group, AS-IV treatment group (PAN+AS-IV group), methylprednisone (MP) treatment group (PAN+MP group), and AS-IV+MP treatment group (PAN+AS-IV+MP group). The model was established by a single tail vein injection of PAN (50 mg/kg body weight). The treatment groups were given 40 mg·kg -1·d -1 AS-IV by intragastric administration and 15 mg·kg -1·d -1 MP by intraperitoneal injection for 10 consecutive days at the same time of modeling. Urine sample was collected on the 11th day of the experiment. The urine protein, urine creatinine and blood albumin were detected by biochemical analyzer. The changes of nephrin and synaptopodin in renal tissues were detected by immunofluorescence assay, and the expressions of nephrin, RhoA and Rac/Cdc42 proteins were detected by Western blotting. Results:Compared with the control group, urine protein creatinine ratio (uPCR) was significantly increased, serum albumin (Alb) was significantly decreased in the PAN group, nephrin expression was significantly down-regulated, and the expressions of RhoA and Rac/Cdc42 were significantly up-regulated in the renal tissue of the PAN group (all P<0.01). Compared with PAN group, serum Alb levels in PAN+AS-IV group and PAN+AS-IV+MP group were significantly increased (both P<0.01), and the uPCR levels in PAN+MP group ( P<0.05) and PAN+AS-IV+MP group ( P<0.01) were significantly decreased (all P<0.05). Compared with the PAN group, the relative expressions of nephrin in renal tissue of all drug intervention group (PAN+AS-IV group, PAN+MP group and PAN+AS-IV+MP group) were significantly increased, while the relative expressions of RhoA and Rac/Cdc42 were significantly decreased (all P<0.01). The immunofluorescence results suggested that the expressions of nephrin and synaptopodin in renal tissue of PAN group were significantly down-regulated compared with the control group, which were reversed in all treatment groups, and the reversion was most pronounced in the PAN+AS-IV+MP group. Conclusion:Both AS-IV and glucocorticoid can improve PAN-induced podocyte injury, and the combination of the two has synergistic action, which may be related to inhibiting the activation of Rho family signaling pathway.