Objective To investigate the protective effects and mechanism of Shenyan 1 Prescription on renal fibrosis of unilateral ureteral obstruction(UUO)rats through TGF-β 1/Smad homologous 3(Smad3)pathway regulating ferroptosis.Methods Totally 48 male SD rats were divided into four groups:sham-operation group,UUO model group,and Shenyan 1 Prescription low-(10 drug/kg),and high-dosage(20 crude drug/kg)groups according to random number table method,with 12 rats in each group.The UUO model was induced by the method of unilateral ureteral obstruction except for those sham-operation group.After modeling,rats received corresponding drugs or normal saline by gavage for 4 weeks,once per day.After 4 weeks,the body mass and the left kidney weight were measured.The 24 h urine protein and the levels of serum albumin(ALB),alanine aminotransferase(ALT),serum creatinine(SCr)and blood urea nitrogen(BUN)were detected by biochemical analysis method;the ROS level in renal tissue was measured using a chemical fluorescence assay kit,and the SOD and MDA levels in left renal tissue of rats were measured using ELISA method;the morphology of renal tissue and the specific blue staining of hemosiderin were observed using HE and Prussian blue staining methods,respectively;the expressions of transforming growth factor-β1(TGF-β1),Smad3,glutathione peroxidase 4(GPX4),and solute carrier family 1 member 5(SLC1A5)were detected by Western blot.Results Compared with the model group,the 24 h urinary protein excretion in Shenyan 1 Prescription high-dosage group decreased(P＜0.05),the serum ALB level increased(P＜0.05),the ALT level decreased(P＜0.05),and the expression of SLC1A5 in renal tissue decreased(P＜0.05);the left kidney weight/body decreased in Shenyan 1 Prescription low-and high-dosage groups(P＜0.05);the levels of serum ROS and MDA decreased(P＜0.05),and the activity of SOD significantly increased(P＜0.05);the expressions of TGF-β1 and Smad3 in renal tissue decreased(P＜0.05),and the expression of GPX4 increased(P＜0.05),and the renal pathological injury and ion deposition were improved.Conclusion Shenyan 1 Prescription has a protective effect on the structure and function of renal tissues in UUO rats through regulating ferroptosis via inhibition of the TGF-β1/Smad3 pathway to inhibit renal fibrosis of UUO rats.
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