Protective Effect Of Rhein On Kidney In Db/db Mice And Podocyte Through Its Influence On Wnt/?-catenin Pathway

Objective: Rhein had been reported in the treatment of diabetic nephropathy.The mechanism of its effects is not clear.Our research started from animals models and cellular model,studied the signaling pathway,Wnt/?-catenin,which is related with epithelial mesenchymal transition(EMT),and studied the injury and apoptosis of podocytes.The role of Rhein in the treatment of diabetic nephropathy was revealed.Methodology: Constructing the DN mice model,using Rhein to intervene podocyte injury,to observe the changes of pathology in diabetic mice kidney,proteinuria,the number and specific mark protein of podocyte,and the protein expression of Wnt/?-catenin signaling pathway.To observe whether high glucose changes podocyte marker protein,wnt/?-catenin signaling pathways and down-stream glycogen synthase kinase with the method of western blotting,real time PCR by culturing human and mouse podocyte in vitro.We used Rhein to parallely intervene podocyte and found out the specific mechanism of Rhein against the podocyte protection.Results: Db/db mice by geven Rhein after 12 weeks of treatment shew weight loss,improvement of hyperlipidemia,hyperglycemia,urinary albumin excretion,and pathological changes.Meanwhile,Rhein inhibited the protein overexpression of wnt/?-catenin signaling(wnt1,p GSK?3?/total GSK?3?,p-?-catenin/total ?-catenin)and improved the decreased expression of nephrin and PPAR-?all of which were caused by renal cortex of db/db mice.High glucose induced morphological changes and upregulated the expression of wnt/?-catenin signaling in cultured mouse podocyte clone 5(MPC5)(P<0.05).The change was more obvious in 48 hours than in 24 hours,which indicated time dependence.Rhein suppressed Wnt/ ?-catenin signaling and upregulated nephrin,PPAR-?in high glucose culture(P<0.05).Conclusions: In vitro and vivo,Rhein could significantly improve the diabetic nephropathy of db/db mice,and suppressed Wnt/ ?-catenin signaling induced by high glucose,which indicates specific mechanism of Rhein against diabetic nephropathy.