The mechanism of Jianpi Gushen Huayu Decoction in the treatment of diabetic kidney disease based on SIRT1/TGF-β1/Smad pathway
[Objective]To investigate the effect of Jianpi Gushen Huayu Decoction(JPGS)in the treatment of diabetic kidney disease(DKD)and the mechanism of JPGS in the treatment of DKD from the direction of epithelial interstitium transition(EMT)and SIRT1/TGF-β1/Smad pathway.[Methods]The 60 C57BL/6J mice were fed adaptive diet for 1 week and HFD for 8 weeks.After STZ modeling,they were randomly divided into normal group(C),model group(M),SIRT1 agonist group(S,50 mg/kg,gavage),low-dose JPGS group(JL,2.4 g/kg,gavage),medium-dose JPGS group(JM,4.8 g/kg,gavage),and high-dose JPGS group(JH,9.6 g/kg,gavage).After 8 weeks of treatment,24 h urine samples,blood samples and kidney tissues of mice were collected for analysis and determination.Levels of 24 h-UPQ,serum Cr and BUN were measured by the kit to evaluate the renal function of mice.The pathological changes of the kidney were observed by HE and Masson staining.RT-qPCR and Western Blot were used to detect the expression of EMT-related factors(E-cad,ZO-1,VIM and α-SMA)to evaluate the effect of JPGS on EMT.Western Blot was used to detect the expressions of SIRT1,TGF-β1,P-Smad2/Smad2 and P-Smad3/Smad3 to evaluate the effect of JPGS on SIRT1/TGF-β1/Smad pathway.[Results]Compared with the model group,the levels of Cr,BUN and 24 h-UPQ in DKD mice treated with JPGS were decreased in varying degrees,the pathological damage of renal tissue was improved in varying degrees,the expression of E-cad and ZO-1 was increased,the expression of VIM and α-SMA was decreased,and the expression of SIRT1 was increased,the expressions of TGF-β1,P-Smad2/Smad2 and P-Smad3/Smad3 were down-regulated.[Conclusion]JPGS inhibited EMT by activating SIRT1/TGF-β1/Smad pathway to alleviate kidney injury in DKD.
万方数据
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