Effect Of Oxidative Stress On The Epithelial-to-mesenchymal Transition Of Tubular Epithelial Cell In Diabetic Nephropathy Rat And The Intervention Study Of Probucol

Beckgroud:Dabetic nephropathy(DN) is a major microvascular complication of diabetes mellitus(DM),which is a leading cause of end stage renal disease(ESRD).There is growing evidence suggests that oxidative stress(OS),epithelial-to-mesenchymal transition(EMT) of tubular epithelial cell and specificity protein 1(Sp1) may play an important role in dabetic nephropathy.However,the mechanisms underlying the role of OS,EMT and Sp1 in DN are not fully understood.Objective:To explore the relation of oxidative stress,Sp1 and the epithelial-to-mesenchymal transition of tubular epithelial cell in diabetic nephropathy rat and the intervention study of probucol.Methods:Thirty SD rats were randomly divided into normal control group(CN),diabetic control group(DN),probucol treatment group(PN). Probucol was given to streptozocin-induced diabetic rats for 12 weeks. Urine protein(UAlb) were evaluated 3 weeks later,and the diabetic nephropathy model were successful established if the UAlb≥30mg/24 h, and collected the UAlb in the 8^th week and the 12^th week.The general state,renal function,renal intrinsic MDA and GSH-Px of rats were also examined in week 12^th.We evaluated the pathology changes and the expression of Sp1,α-SMA and E-cadherin in each slice with immunityhistochemistry and western blot.Results:Compare to the CN group,the blood sugar(BS),serum Cr and Ualb increased observably in the rats of DN group(P＜0.01),the CCr reduced(P＜0.01).The levels of MDA in renal intrinsic in DN group was higher than in CN group and PN group(P＜0.001).The pathological scores and the expression of Sp1 andα-SMA in renal tissue were higher in the DN animals than that in the other animals(P＜0.001),the expression of E-cadherin was lower in the DN animals than that in the other animals(P＜0.001).The MDA level in each group was positive correlation to the expression of Sp1 andα-SMA(γ=0.862,P＜0.001;γ= 0.896,P＜0.001,respectively),and negative correlation to the expression of E-cadherin(γ=-0.673,P＜0.001).The SCr,CCr,Ualb,MDA level,pathological scores of renal tubule and the expression of Sp1 andα-SMA in renal tissue in PN group were alleviated than in DN group(P＜0.001), the expression of E-cadherin was increased obviously(P＜0.001),and no increase in the levels of such index was observed compared to CN group(P＞0.05).Conclusion:The level of oxidative stress in STZ-induced diabetic nephropathy rats was increased.Oxidative stress played an important role in the early stage of epithelial-to-mesenchymal transition of tubular epithelial cells in diabetic nephropathy rats.Sp1 might play a role in the epithelial-to-mesenchymal transition of tubular epithelial cells induced by oxidative stress in diabetic nephropathy rats.Probucol play a protect role in diabetic nephropathy,which was related to anti-oxidant and suppress the expression of Sp1 and the epithetial-to-mesenchymal transition of tubular epithelial cells in diabetic nephropathy rats.