Effects of Canagliflozin Combined with Amiloride and Benzamil in Rats with Doxorubicin-induced Nephrotic Syndrome
Objective To investigate the effects of canagliflozin combined with amiloride and benzamir on doxorubicin-induced ne-phrotic syndrome(NS)model rats.Methods A total of 49male SD rats were randomly divided into 7groups:normal control group(NG group),model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),cana-gliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 rats in each group.The NS model was established by injection of doxorubicin in the tail vein.The 24h-UTP of each group was detected one day before treatment to verify the successful preparation of the model.Each group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.After 6 weeks of treatment,the 24h-UTP,UNa,UK,UCl levels in urine and the albumin(ALB),triglyceride(TG),total cholesterol(TC),low density lipopro-tein(LDL),Urea,Crea,CysC,SNa,SK,SCl levels in serum were measured,respectively.The expression of serum transforming growth factor-β1(TGF-β1)and soluble thrombomodulin(sTM)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TGF-β1 gene was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The renal pathology of rats in each group were tested by the hematoxylin-eosin(HE)staining and Masson staining.Results After successful modeling,the levels of 24h-UTP,TG,TC,LDL in the MG group were increased,while the levels of ALB was decreased(P＜0.05).After 6 weeks of drug intervention,compared with MG group,the levels of 24h-UTP,TC,TG,LDL were decreased,and the level of ALB was increased in all drug groups(P＜0.05),and the level of TGF-β1 was decreased in the KG group(P＜0.05),and the levels of CysC,UNa,TGF-β1,sTM was increased in the KA group(P＜0.05).The results of HE staining and Masson staining showed that typical characteristics of focal segmental glomerulosclerosis appeared in the renal tissue of rats in MG group,all drug groups were observed in varying degrees of improvement.Conclusion Canagliflozin,benzamil,amiloride alone and canagliflozin combined with benzatrimil and amiloride could improve the macroproteinuria,hypoproteinemia and hyperlipidemia of doxorubicin-induced NS model rats.Canagli-flozin alone can effectively reduce TGF-β1 expression and thereby reduce kidney inflammation,but the combination of canagliflozin and amiloride may cause renal insufficiency and endothelial injury.
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