Expression And Significance Of SOD2in Renal Tissues Of IMN Patients

Objective: Membranous nephropathy (MN) is one of the most commonpathological types of nephrotic syndrome (NS) in adults. According tostatistics, idiopathic membranous nephropathy (IMN) nearly takes up about75%. And the others occur secondary to a variety of reasons, including cancer,infection, autoimmune disease, metabolic disease, drug toxic damage, and soon. About1/4-1/3of IMN patients can relieve completely or partly. Thespontaneously remissive IMN patients with macro-proteinuria (≥3.5g/24h)can account for about20%. And the rest of the patients will progress toend-stage kidney disease slowly, or die of the complications and other diseasesin5-16years. In recent years, although the morbidity of IMN is rising year byyear, its pathogenesis is still unclear. So it is important to make thepathogenesis clear and it will be helpful to IMN’s diagnosis and treatment.Manganese superoxide dismutase (SOD2) is a kind of antioxidant metalenzyme, which is a main part of the wide range of antioxidant cell protectionsystem. Toxicity superoxide anion can be converted to hydrogen peroxide anddiatomic oxygen by SOD2. SOD2plays a crucial role in the oxidation andantioxidant balance of the body. When the body suffering from variousharmful stimuli, highly reactive molecules will be produced overmuch in thebody, which makes oxidation and anti-oxidation system out of balance, andmakes the body in oxidative stress (oxidative stress, OS). OS is closelyconnected with the occurrence and development of many diseases, especiallyin the process of kidney diseases. SOD2expresses increased under OS state, itcould reduce the damage to organization by OS. There are various damagemarkers of OS.8-hydroxy-2’-deoxyguanosine (8-OHdG) is a sensitive markerfor DNA damage. Under the stimulation of some exogenous substances ordiseases, reactive oxygen class (ROS) releases immediately and stores excessively in the body. When OS is beyond the body’s antioxidant capacity, itmay cause the oxidative damage of DNA. Another study found that SOD2may be a specific antigen of podocytes in IMN renal tissues, and it promotesthe progress of IMN. So it is necessary to study the expression level of SOD2in IMN patients’ renal tissues. The research will study the expression and thesignificance of SOD2in renal tissues of IMN patients, and analyze therelationship between SOD2and IgG4in renal tissues. At the same time, wealso test the level of8-OHdG in patients’ serum and urine specimens. Finally,we explore the role of OS in the pathogenesis of IMN, reveal the pathogenesisof IMN, and provide the basis for guiding clinical treatment and observingprognosis.Methods:41IMN patients were from the nephrology department of thethird hospital of Hebei Medical University, which were diagnosed as IMN byrenal biopsy between June2013and December2013. We collected13hospitalized patients of secondary membranous nephropathy (SMN) and6hospitalized patients of minimal change disease (MCD) as the control groups.They all received renal biopsy for the first time. Immunohistochemistrymethod was used to detect the expression position of SOD2and IgG4in renaltissues in IMN group, SMN group and MCD group. The result has beensemi-quantitative analyzed by image analysis system (Image-ProPlus, IPP).At the same time, serum and urine samples were collected in the morning,which came from the patients of every group. We also detected the expressionlevel of8-OHdG in serum and urine specimens with ELISA quantitativemethod. And the relationship between SOD2and8-OHdG has been discussed.The experimental data have been treated by statistical software SPSS17.0. Itis statistically significant when P is less than0.05. We use x±s (mean±standard deviation) to show the measurement data. And count data areshowed by rate or constituent ratio. The comparison of mean of normaldistribution data is analyzed by One-Way ANOVA among groups, and multiplecomparisons of means is done by SNK-q test. The correlation is tested withthe linear correlation analysis. Results: SOD2expressed no difference in renal tubular epithelial cells ofSMN group, MCD group and IMN group; SOD2did not expressed inglomeruli of SMN group and MCD group; SOD2expressed in renalglomerular basement membrane, podocyte and sub-epithelium of renal tissuesin IMN group. In IMN group, the expression of SOD2in glomeruli was muchmore than that in SMN and MCD group (P<0.01). There was no IgG4expression in SMN and MCD group; IgG4expressed in renal glomerularbasement membrane and sub-epithelium of renal tissues in most of IMNpatients. The expression of IgG4was much more intensive in glomeruli ofIMN group than in glomeruli of SMN and MCD group (P<0.01). In IMNpatients, we found a negative correlation between SOD2and24hours urinaryprotein (r=-0.354, P=0.023, P<0.05); There was a positive correlation betweenIgG4and24hours urinary protein (r=0.361, P=0.021, P<0.05). The8-OHdGin serum and urine of IMN and SMN groups expressed more than MCD group(P<0.05), and has no statistically significant difference between IMN andSMN group (P>0.05).Conclusion: The rising expression of8-OHdG in serum and urine inpatients of IMN show us that there is DNA oxidative damage in IMN andoxidative stress may be involved in the occurrence and development of IMN.SOD2expresses increased in IMN renal tissues and have a negativecorrelation with24hours urinary protein, which reminder that SOD2plays animportant role to protect the body in renal oxidative stress and reduce theurinary protein. But SOD2and IgG4both deposit under glomerular epitheliumof IMN renal tissues. It is suggested that SOD2may be a pathogenic antigenof podocytes and take part in the process of IMN.The expression level of SOD2is different in IMN and SMN, whichprompts the different pathogenesis of IMN and SMN.