The Expression Level Of Toll Like Receptor4in The Renal Tissue Of Patients With Diabetic Nephropathy And The Effect Of ARB On The Expression

Objective:1.By researching the expression level of toll-like receptor4, and its adaptorMyD88, nuclear factor B, as well as MCP-1、TNF-α in patients with diabeticnephropathy and their relationships, in order to explore the role of TLR4signalingpathways in the pathogenesis of diabetic nephropathy.2. By comparing the level of TLR4and the downstream signaling molecules ofARB and DN groups, to explore the therapeutic effect of inhibiting TLR4signalingpathways of DN and revealing the new mechanism of ARB in the treatment of DN.Methods:The search objects were divided into diabetic nephropathy group (DN), ARBgroup (ARB) and normal control group (NC).32cases of diabetic nephropathy groupwere diagnosed of DN patients by kidney pathological biopsy, from the first affiliatedhospital of Nanchang university renal medicine in February2012to February2013,and nearly4weeks using ARB therapy and unused ARB therapy of the patients weredivided into2groups, respectively, DN group (20cases) and ARB roup (12cases).Control group included5patients,who were from the same hospital urology in thesame period with renal resection. We observed the pathological changes of kidneytissues and the levels of TLR4、MyD88、NF-B、MCP-1、TNF-α in kidney tissuesby HE, Masson, PAS, PASM staining kidney pathological and immunohistochemicalmethod.We collected patients’ serum creatinine, serum albumin, fasting plasmaglucose, postprandial2hours blood glucose, glycosylated hemoglobin,24hoursurinary protein quantitative, CRP, and recorded the patients’ blood pressure,andanalyzed the relationship between TLR4andMyD88、NF-B、MCP-1、TNF-α.Results:1. The renal histopathologic biopsy: In NC group，glomerular and renal tubularof NC group were not obvious changes. Capillary ball hypertrophy, basementmembrane mildly thick, mesangial matrix mildly hyperplasia, renal tubular epithelial cells showed cavity and granular degeneration,of ARB group, diffuse thickening ofthe glomerular basement membrane, mesangial matrix proliferation.even some of theglomerular mesangial matrix severe hyperplasia, formation of tuberous sclerosis ofDN group.2. Clinical and biochemical index results: The serum creatinine,serum ureanitrogen and24hours urine protein quantitatively, the CRP level of DN group ishigher than the NC group and ARB group (P <0.05), the ARB group is higher thanthe NC group (P <0.05);The level of serum albumin and Ccr of DN group and ARBgroup were lower than NC group (P <0.05),DN group was lower than ARB group(P<0.05).3. Immunohistochemical results: TLR4，MyD88，NF-B，MCP-1,TNF-α werealmost no expression in renal tissue of the NC group; The expression in DN and ARBgroup was higher than in the NC group (P <0.05),The expression in DN group werehigher than in the ARB group (P <0.05).4. The expression level of TLR4were positively correlated with the level ofMyD88，NF-B，MCP-1，TNF-α (r were0.940,0.963,0.934,0.929, P <0.05).Theexpression level of TLR4and the levels of serum creatinine,urine proteinquantitative,CRP and Ccr had correlation(r were0.874,0.958,0.908,-0.676, P <0.05)Conclusion:1.The expression of TLR4and downstream signaling molecules were raised andthey were related with each other,prompting TLR4signaling pathway activation maybe the pathogenesis of diabetic nephropathy important factor.2.The levels ofTLR4,MyD88,NF-B,MCP-1,TNF-α of DN group were higher than ARBgroup,suggesting that kidney RAS may be associated with TLR4signaling pathwaysactivated and block TLR4signaling pathway may be a new method for treatment ofDN inflammatory reaction.