Protective Effect Of TNF-? Inhibition On Diabetic Nephropathy In Rats

Background:Diabetic nephropathy is the second-leading cause of end-stage renal disease in China,and the most important cause of end-stage renal disease in Europe and America.Although Glomerulosclerosis is recognized as a primary feature of DN,tubular injury in DN(described as diabetic tubulopathy)is closely associated with increased risk of renal function decline,which is essential for the occurrence and development of diabetic nephropathy.Current therapies used to treat DN do not combat tubular injury.This study was conducted to investigate whether TNF-? inhibition protects againstdiabetic tubulopathy and examine the associated mechanisms.Methods:Male SD rats were randomly divided into four groups(6 rats in each group):normal control,STZ-induced diabetes,STZ-induced diabetes+control IgG,STZ-induced diabetes+TNF ? inhibitor(Adalimumab).Rats was treated once a week for 12 weeks.At the end of the experiment,24-hour urine was collected in metabolic cage,and serum and kidney tissues were collected for analysis.Blood glucose,Serum creatinine,proteinuria,histological alterations,TNF-? and NLRP3 inflammasome were assessed.Results:TNF-? inhibition had no influence on blood glucose and HbAlc,and there was no significant difference in serum urea nitrogen and creatinine between IgG control and TNF ? inhibition.Compared with IgG control,TNF ? inhibition can reduce renal weight index and albuminuria.TNF ? inhibition decreased glomerular mesangial index and renal tubular injury score in DN rats.Compared with IgG control,TNF ? inhibition significantly reduced serum CRP and decreased TGF-?1 and P-selectin.TNF ? inhibition decreased MDA and increased SOD levels in kidney tissue.Compared with the control group,the levels of IL-10 and NLRP3 inflammasome in glomeruli and tubulopathy of DN rats increased.TNF-? inhibition significantly reduced IL-1? and NLRP3 inflammasome in glomeruli and tubulopathy.Conclusions:TNF-? inhibition could attenuate diabetic renal tubulopathy by inhibiting the NLRP3 inflammasome in diabetic rats.