淡豆豉异黄酮调控TGF-β1/SnoN通路对糖尿病肾病小鼠肾组织的保护作用研究OACSTPCD

[Objective]To observe the protective effect of isoflavones in fermented soybean on renal tissues in diabetic kidney disease(DKD)mice and to explore its regulation effect on transforming growth factor-β1(TGF-β1)/Smad nuclear transcription co inhibitor(SnoN)signal pathway.[Methods]The 50 SPF db/db mice and 10 SPF db/m mice were included,and the former were randomly divided into 5 groups after successful DKD modeling validation,and the latter was recorded as control group.The enalapril group was given enalapril 10mg/kg dissolved in 0.1 ml/kg normal saline by gavage,and the isoflavones in fermented soybean low,medium and high dose groups were given 12.5 mg/kg,25 mg/kg and 50 mg/kg isoflavones in fermented soybean dissolved in normal saline by gavage,while the other groups were given normal saline by gavage.They were intervened once a day for 8 weeks.Fasting blood glucose(FBG)was detected by hexokinase method before intervention,4 weeks after intervention and after intervention,and 24-hour urine protein were detected by quantitative protein analysis(BCA).Serum creatinine(Scr),blood urea nitrogen(BUN)and TGF-β1 levels were detected.After intervention,the mice were killed and the renal tissues were taken.The pathological changes of renal tissues were observed.Real time reverse transcription polymerase chain reaction(RT-qPCR)was used to detect the expressions of TGF-β1,Smad2/3,Smad7 and SnoN mRNA.The protein expressions of TGF-β1,Smad2/3,Smad7,SnoN and phosphorylation of Smad2/3(p-Smad2/3)were detected.[Results]FBG,24 h urine protein,Scr,BUN and TGF-β1 in model group after 4 weeks and the whole process intervention were higher than those in the normal group,and the 24 h urine protein,SCR,BUN and TGF-β1 in the enalapril group and isoflavones in fermented soybean low,medium and high dose groups were lower than those in the model group(P＜0.05).In the model group,the renal tissue showed significant pathological changes.The pathological changes and collagen fiber deposition were alleviated in the enalapril group and isoflavones in fermented soybean low,medium and high dose groups.TGF-[31 mRNA and protein expressions,Smad2/3 mRNA expression and p-Smad2/3 levels in the model group increased(P＜0.05),which in the enalapril group and isoflavones in fermented soybean low,medium and high dose groups were lower than those in the model group(P＜0.05).Smad7,SnoN expressions in the model group decreased(P＜0.05),which in the enalapril group and isoflavones in fermented soybean low,medium and high dose groups were higher than those in the model group(P＜0.05).The effect of isoflavones in fermented soybean low,medium and high dose groups was dose-dependent.Except FBG,there was no significant difference in the above quantitative indexes between the isoflavones in fermented soybean dose group and enalapril group(P＞0.05).[Conclusion]Isoflavones in fermented soybean can lower blood glucose,reduce 24 h urinary protein,protect renal function,reduce serum TGF-β1 level,alleviate kidney illness,lower the expression of TGF-βi and Smad2/3,reduce p-Smad2/3 level,and promote the expression of Smad7 and SnoN in DKD mice.