The Expression Of Toll Like Receptor 4 And Its Associated Inflammatory Factors In Renal Tubular In Human Diabetic Nephropathy

Objective:Researches show that the expression of inflammatory factors in renal tubular could be induced by proteinuria,those could injury the tubular in different ways.We have proved that the expression of inflammatory factors such as NF-кB, MCP-1 and OPN increased in renal tubular in human diabetic nephropathy(DN),and were correlated with the degree of proteinuira and renal function.It suggested that the expression of inflammatory factors in renal tubular was important to the progression of DN.But it is unclear about the mechanism that stimulates the inflammatory reaction.TLR4 is an important regulation factor in immunity reaction.It could regulate the expression of NF-кB,MCP-1 and OPN,to stimulate the immunity and inflammatory reaction.The present study identified the expression changes in TLR4, NF-кB,MCP-1 and OPN in patients with diabetic nephropathy,to investigated the correlations between TLR4 and the clinical parameters findings,such as proteinuira and renal function.Method:The experimental group:34 patients were diagnosed DN by renal biopsy, who were admitted in our hospital between January,2006 and January,2007.The control group:10 patients with renal carcinoma who underwent nephrectomy admitted in our hospital in the corresponding time.Clinical presentations,such as urinary N-acetylglucosaminedase(NAG),proteinuira,serum creatinine,glycosylated hemoglobin and immunohistochemical findings for the expressions in TLR4,NF-кB, MCP-1 and OPN were assembled.To investigate the correlations between these clinico-pathological findings and TLR4 in Pearson correlation coefficient.Results:1.The renal pathological findings showed that nonspecific tubulointerstitial change was found in control group.In contrast,among all 34 patients with DN,the inflammation responses were apparent,such as granular degenerationand focal wither in tubular epithelial cell,infiltration of inflammatory cells,interstitial fibrosis, thickened-wall and narrowed-lumina in arteriole,which directly related to the progression of DN.2.The degree of proteinuira,serum creatinine,N-acetylglucosaminedase and glycosylated hemoglobin in DN were higher than the controls,which were correlated significantly with the progression of DN.3.Immunohistochemistry assay showed no expression in TLR4,NF-кB,MCP-1 and OPN in the controls.In DN group,TLR4,NF-кB,MCP-1 and OPN located mainly in proximal renal tubular epithelial cell,and tenuous in glomcrulus and renal interstitium.The expression increased with the degree of proteinuria.4.The expression of TLR4 was correlated significantly with the level of NF-кB, MCP-1,OPN,proteinuria,serum creatinine,N-acetylglucosaminedase and glycosylatedhemoglobin(r=0.900,0.895,0.880,0.802,0.485,0.757,0.612,P＜0.05).Conclusion:1.The expression of TLR4 in renal tubular increased in DN,and was correlated significantly with NF-кB,MCP-1,OPN.It suggested that the increased expression of TLR4 may play an important role in the inflammation reaction in the renal tubular.2.In DN the expression of TLR4 was correlated significantly with the proteinuria.It indicated that proteinuria may be the cause of the increased expression of TLR4.3.In DN the expression of TLR4,NF-кB,MCP-1,OPN was correlated significantly with the renal function.It suggested that the inflammation reaction in the renal tubular play an important role in the progression of DN.