Jaceosidin regulates the inflammatory response in rats with diabetic nephropathy by the SIRT1/FoxO3 signaling pathway
This study aims to investigate the influence of jaceosidin on inflammatory response in diabetic nephropathy(DN)rats.Male SD rats were randomly divided into control group,model group,low(10 mg/kg)and high(20 mg/kg)dose jaceosidin groups,positive control group(500 mg/kg metformin),and inhibitor group(20 mg/kg jaceosidin+5 mg/kg silent mating-type information regulation 2 homolog 1[SIRT1]inhibitor EX-527),with 12 animals in each group.Except for the control group,all rats were fed with high-fat diet combined with chemical induction to establish the rat DN model.After the model was successfully established,animals were treated with drugs by gavage,once a day for four weeks.Kidney function changes were detected by microplate reader and the expressions of inflammatory factors were detected by ELISA.The pathological changes of the kidney were examined by H-E staining and the expressions of nephrin and podocin in renal tissues were detected by immunohistochemistry.The expressions of SIRT1/forkhead box protein O3(FoxO3)signaling pathway-related proteins in renal tissues were detected by Western blotting.The results showed that compared to the control group,the model group showed obvious interstitial inflammatory infiltration,glomerular hypertrophy,and vacuolar degeneration of renal tubular cells,impaired kidney functions,serum inflammatory factors and FoxO3 expression were significantly increased,while the nephrin,podocin,and phosphorylated SIRT1(p-SIRT1)/SIRT1 expression levels were significantly decreased(P＜0.05).Compared to that of the model group,the pathological injury of the renal tissues in the low-dose and high-dose jaceosidin groups and the positive control group was significantly improved,and kidney functions were restored,while serum inflammatory factors and FoxO3 expression were significantly decreased,while the expressions of nephrin,podocin,and p-SIRT1/SIRT1 were significantly increased(P＜0.05).Adding SIRT1 inhibitor EX-527 attenuated the anti-inflammatory effect of jaceosidin.The study suggests that jaceosidin can alleviate inflammatory response in DN rats by regulating the SIRT1/FoxO3 signaling pathway.
diabetic nephropathyjaceosidinsilent mating-type information regulation 2 homolog 1forkhead box protein O3inflammatory response
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