Xylitol Alleviates Renal Injury in Type 2 Diabetes Mellitus Mice by Modulating PI3K/Akt/FoxO1/NFF-κB Signaling Pathway
Objective It is to investigate the mechanism of xylitol in ameliorating renal injury in mice with type 2 diabetes mellitus(T2DM).Methods Mice were randomly divided into four groups:normal control group(NC),diabetes control group(DC),10％xylitol group(DX10),and 20％xylitol group(DX20),with 6 mice in each group(ni=6).To establish a mouse model of T2DM,all mice were administered 40 mg/kg streptozotocin,except for the NC group.After modeling,different ratios of xyli-tol was added to the normal feed and administered continuously for 8 weeks.Fasting blood glucose(FBG)levels were measured;serum levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were determined by ELISA;renal tissues were colorimetrically assayed for catalase(CAT),malondialde-hyde(MDA)and total antioxidant capacity(T-AOC);morphologic changes were observed by H-E stai-ning;and Western-blot was used to detect the protein expressions of p-PI3K,PI3K,p-Akt,Akt,p-FoxO1,FoxO1,nuclear factor Kappa-B(NF-κB),intercellular adhesion molecule-1(ICAM-1),Bcl-2,and Bax in renal tissues.Results(1)Compared to the NC group,FBG levels were increased in the DC group(P＜0.01)and decreased after xylitol intervention,and the decrease was more significant in the DX20 group than in the DX10 group(P＜0.05);(2)Serum levels of IL-6 and TNF-α in DC group was higher than that in NC group(P＜0.000 1),and both were decreased after xylitol intervention,and the decrease was more significant in the DX20 group than in the DX10(P＜0.000 1);(3)Compared to the NC group,CAT and T-AOC was decreased,and MDA was increased(P＜0.01)in the DC group,and after xylitol intervention,CAT and T-AOC were increased,while MDA was decreased(P＜0.05),and more significantly in the DX20 group than in the DX10 group(P＜0.05);(4)H-E staining showed that xylitol intervention improved diabetic kidney injury,and the DX20 group was more effective than the DX10 group(P＜0.05);(5)Western-blot showed that the expression of p-PI3K,p-Akt,p-FoxO1 and the ratio of Bcl-2/Bax decreased,compared with the NC group(P＜0.000 1,P＜0.001,P＜0.01,P＜0.001),and NF-κB nuclear translocation and ICAM-1 were increased in renal tissue of the DC group(P＜0.000 1,P＜0.01).Compared with the DC group,the xylitol intervention reversed the changes of the relevant proteins,and it was more significant in the DX20 group than the DX10 group(P＜0.05).Conclusion Xylitol ameliorates renal injury in T2DM mice through activating the PI3K/Akt/FoxO1 signaling pathway and inhibiting NF-κB signaling pathway.
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