Expression Of Oxidative Stress Related Factors In Idiopathic Membranous Nephropathy

Background:Membranous nephropathy(MN)or membranous glomerulonephritis,a glomerular disease,is one of the common causes of adult nephrotic syndrome.Its histopathological manifestations is the immune complexes deposition under glomerular epithelial cells and diffuse thickening ofglomerular basement membrane(GBM)in most patients.Approximately 75% of MN patients are idiopathic membranous nephropathy(IMN)in developed countries,and other membranous nephropathy are associated with seconddiseases,such as,autoimmune diseases,hepatitis B or Hepatitis C virus and other chronic infections,previously exposuring to drugs or toxins,and malignant tumors.It is thought that idiopathic membranous nephropathy is an organ-specific autoimmune disease.The clinical prognosis of this disease is quite different.Spontaneous remissions are very common in children,and there are 25-30% of patients can spontaneously relieve in adults;However,about10% to 40% of patients willprogress to end-stage renal disease(end-stage renal disease,ERSD)after 10 years.the remaining patients showe persistent proteinuria,but renal function keep relatively stable.Previously relevant datas show that IMN accounts for about 9.89% to 13.3% of primary glomerulonephritis.In recent years,in a retrospective study(2005-2010),IMN had become the second largest pathological type of primary glomerular disease,accounting for 27.5%,more than twice the past decade.Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage Oxidative stress.Itcan occur when the production of reactive oxygen species(ROS)aremore than the antioxidant defenses or when the antioxidant defenses activity are reduced or the antioxidant defenses are reduced.When the body is subjected to harmful stimuli,a large number of ROS will be produced,which aremore than the body's ability to clear.Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell,including proteins,lipids,and DNA.Superoxide dismutase(SOD)?heme oxygenase(HO-1)are currently well recognized antioxidant markers and scavengers of oxygen free radicals,which can remove the superoxide anion radicals in the body.Malondialdehyde(malondiadehyde,MDA)is formed because of polyunsaturated lipids are degraded by reactive oxygen species when the body are stimulated by harmful attacks;8-Hydroxy-2'-deoxyguanosine(8-OHdG)is one of the major products of DNA oxidation.they are markers that reflect the degree of lipid and DNA oxidative damage in vivo.At present,the role of oxidative stress in renal diseases such as hypertensive nephropathy,diabetic nephropathy,interstitial nephritis and acute renal injury has been confirmed by many studies,but the role of oxidative stress in the pathogenesis of IMN is not yet elucidated.Purpose:1.To explore the urine expression of oxidative stress-related factors SOD,HO-1,MDA and 8-OHdG inIMN,secondary membranous nephropathy(SMN),minimal change nephropathy(MCD)and normal Control groups(normal control,NC).2.To investigate the expression of oxidative stress-related factors SOD,HO-1,8-OHdG in renal tissues of IMN,SMN,MCD and NC groups;3.To investigate the relationship between oxidative stress-related factors SOD,HO-1,MDA,8-OhdG and pathogenesis of idiopathic membranous nephropathy.Method:Forty patients with idiopathic membranous nephropathy(IMN),twenty patients with minimal change disease and(MCD)and twenty patients with second membranous nephropathy who were admitted to the Department of Nephrology,the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2016,were enrolled in this study.these patients were firstly diagnosed by renal biopsy,and did not use immunosuppressive therapy before the biopsy.Six normal renal tissues were gotd from renal tumor resection,and 20 healthy subjects were treatedas the control group.The expression of oxidative stress-related factors SOD,H0-1,8-OHdG in renal tissue was detected by immunohistochemical method.The distribution of oxidative stress-related factors in glomeruli and tubules was analyzed.The expression of SOD,HO-1,MDA and 8-OHdG in blood and urine samples were detected by ELISA,and the expression intensity of these factors in each group was analyzed.The correlation between oxidative stress related factors and urinary protein creatorine ratio(uPCR)was ananlyzed in IMN group.Result:1.The distribution and expression of oxidative stress-related factors SOD,HO-1and 8-OHdG in renal tissues were measured by immunohistochemistry.The results showed that SOD was expressed in renal tubules and glomeruli,and the expression of SOD in renal tubules was significantly higher than that in glomeruli.Compared with NC group,the expression of SOD in IMN group and SMN group was significantly higher than that in NC group(P <0.05)(P> 0.05)??.There was no significant difference between the IMN group and the SMN group(P> 0.05).The expression of HO-1 in IMN group and SMN group was significantly higher than that in MCD group and NC group(P <0.05).There was no significant difference between IMN group and SMN group(P> 0.05).8-OHdG mainly expressed in the glomeruli and renal tubules cellsnucleus,less expression in the cytoplasm.its expression in IMN and SMN group was significantly higher than that in the MCD group and NC group,.Its expressionin the IMN group and SMN group had no significant difference(P> 0.05).2.The expression of SOD,HO-1,MDA and 8-OHdG in blood and urine samples were detected by ELISA.SOD in IMN group was significantly higher than that in MN group and NC group(P <0.01).The expression of SOD in IMN group was higher than that in NC group(P <0.01)<0.01)??,and in SMN and MCD group,there were no significant statistical significance(P> 0.05);The expression of HO-1,MDA and 8-OHdG in IMN group were significantly higher than those in MCD and NC group(P <0.05),but there was no significant difference between SMN group and SMN group(P> 0.05);There was no significant expression difference between the MCD and NC group(P> 0.05).The expression of HO-1,MDA and 8-OHdG in the urine of IMN group was also significantly different from that in SMN group(P>0.05),which was higher than that in MCD and NC group(P <0.05)(P <0.05)??,and the expression was also higher than that in NC group(P <0.05).3.The relation between expression of SOD,8-OHdG,HO-1 and MDA in the urine of the IMN group and urinary protein / creatinine(uPCR)was analyzed by Pearson correlation.HO-1 and SOD were not significantly correlated with uPCR and8-OHdG and MDA were positively correlated with uPCR.Conclusion:1.The expressions of SOD,8-OHdG,HO-1 and MDA in IMN patient were increased.2.Oxidative stress can lead to lipid,DNA,protein oxidative damage.3.Oxidative stress is closely related to clinical practice,and to a certain extent,confirming the oxidative stress was involved in the pathogenesis of IMN.