Expression Level And Clinical Significance Of S100A8,S100A9 And TLR4 In Chronic Nephritis

Objective:S100A8 and S100A9 are damage-associated molecular patterns（DAMPs）proteins that have been shown to play important roles in a variety of inflammatory diseases,tumors and autoimmune diseases.In this study,the expression levels of S100A8 and S100A9 proteins in chronic glomerulonephritis were studied.And the pathogenesis of chronic glomerulonephritis.Methods:A total of 70 patients with chronic nephritis from the Affiliated Hospital of Guangxi Medical University were selected and divided into 30patients with chronic nephritis group A（CKD1～2）.Chronic nephritis group B included 40 patients with chronic nephritis of CKD stage 3～5.And 20 healthy subjects as normal control group.Serum S100A8 and S100A9 protein expression levels of the experimental groups and the normal control group were detected by enzyme-linked immunosorbent assay（ELISA）.Flow cytometry（FCM）method was used to detect the expression of Toll-like receptor 4 in each experimental group.The relevant examination data（blood urea nitrogen,blood creatinine,uric acid,cystatin C,HCO₃^-,retinol binding protein,white blood cell count,hemoglobin concentration,platelet count,monocytes,neutrophils,and lymphocytes）of the subjects at admission were counted and analyzed.Meanwhile,the relationship between S100A8,S100A9 proteins and Toll-like receptor 4 was analyzed.Results:1.The expression level of S100A8 protein concentration in chronic glomerulonephritis（18.233±8.923）ng/ml was significantly higher than that in normal control group（4.319±3.042）ng/ml,with statistical significance（P<0.05）.The expression of chronic nephritis in group A（13.765±6.122）ng/ml was higher than that in normal control group（4.319±3.042）ng/ml,and the difference was statistically significant（P<0.05）.The expression of 18.873±9.392ng/ml in group B was higher than that in normal control group（4.319±3.042）ng/ml,and the difference was statistically significant（P<0.05）.The expression level of chronic nephritis group B（18.873±9.392）ng/ml was higher than that of chronic kidney group A（13.765±6.122）ng/ml in CKD3-5 stage,and the difference was statistically significant（P<0.05）.2.The expression level of S100A9 protein in chronic glomerulonephritis（101.442±59.725）ng/m L was significantly higher than that in normal control group（25.74±11.620）ng/m L,and the difference was statistically significant（P<0.05）.The expression level of chronic nephritis group A（59.742±22.743）ng/ml was significantly higher than that of normal control group（25.74±11.620）ng/ml,and the difference was statistically significant（P<0.05）.The expression level of chronic nephritis group B（112.321±62.406）ng/ml was higher than that of normal control group（25.74±11.620）ng/ml,and the difference was statistically significant（P<0.05）.The expression level of chronic nephritis group B（112.32±62.41）ng/ml was higher than that of chronic nephritis group A（59.74±22.74）ng/ml,and the difference was statistically significant（P<0.05）.3.Correlation analysis of S100A8 and S100A9 showed that S100A8 was significantly positively correlated with S100A9（r=0.543,P<0.05）.With the progression of the disease,the protein expressions of S100A8 and S100A9 were up-regulated more obviously,and the differences were statistically significant（all P<0.05）.4.Correlation analysis of the protein expression levels of S100A8 and S100A9with blood urea nitrogen,blood creatinine,uric acid,cystatin C,retinol binding protein,white blood cell count,hemoglobin,platelet count,monocytes,neutrophils and lymphocytes,in which the protein expression levels of S100A8and S100A9 were all correlated with blood urea nitrogen,blood creatinine,uric acid,There was a positive correlation between cystatin C and retinol binding protein（P<0.05）.The expression level of S100A9 protein was negatively correlated with HCO₃^-（P<0.05）.S100A8 and S100A9 proteins were not correlated with WBC count,hemoglobin concentration,platelet count,monocytes,neutrophils and lymphocytes（all P>0.05）.5.There was no significant difference in TLR4 positive expression rate between chronic glomerulonephritis patients（26.196±20.797%）and normal control group（32.755±20.275%）（P>0.05）.There was no significant difference in TLR4positive expression rate between chronic nephritis group A（28.787±23.290%）and chronic nephritis group B（24.900±19.727%）（P>0.05）.The positive expression rate of TLR4 in chronic nephritis group A（28.787±23.290%）was not significantly different from that in normal control group（32.755±20.275%）（P>0.05）.the positive expression rate of TLR4 in chronic nephritis group B（24.900±19.727%）was not significantly different from that in normal control group（32.755±20.275%）（P>0.05）.6.The correlation analysis between TLR4 and serum S100A8 protein showed that TLR4 was positively correlated with serum S100A8（r=0.265,P=0.048）,while serum S100A9 was not correlated with TLR4（r=0.063,P=0.643）.7.By analyzing the correlation between TLR4 and blood urea nitrogen,blood creatinine,uric acid,HCO₃^-,cystatin C,retinol binding protein,white blood cell count,hemoglobin concentration,platelet count,monocytes,neutrophils and lymphocytes,The results showed that TLR4 had no significant correlation with blood urea nitrogen,serum creatinine,uric acid,HCO₃^-,cystatin C,retinol binding protein,white blood cell count,hemoglobin,platelet count,monocytes,neutrophils and lymphocytes（all P>0.05）.Conclusion:1.The high expression levels of S100A8 and S100A9 proteins in serum of patients with chronic glomerulonephritis suggest that S100A8 and S100A9proteins may be involved in the occurrence and development of chronic glomerulonephritis.2.The protein expression levels of S100A8 and S100A9 in group B of chronic nephritis were higher than those in group A of chronic nephritis,suggesting that S100A8 and S100A9 are related to the severity of chronic nephritis.Dynamic detection of serum S100A8 and S100A9 protein levels in patients with chronic nephritis is helpful to understand the extent of kidney injury in patients with chronic nephritis,and provides guidance for the judgment of disease treatment or prognosis（area under the ROC curve of S100A8 protein is 0.977;Area under the ROC curve of S100A9 protein was 0.954）.3.S100A8 protein was positively correlated with S100A9 protein.4.The protein expression levels of S100A8 and S100A9 were positively correlated with blood urea nitrogen,serum creatinine,uric acid,cystatin C and retinol-binding protein.The expression level of S100A9 protein was negatively correlated with HCO₃^-.S100A8 and S100A9 proteins had no correlation with WBC count,hemoglobin concentration,platelet count,monocytes,neutrophils and lymphocytes.5.There was no difference in the positive expression rate of TLR4 between chronic glomerulonephritis and normal controls,or between chronic nephritis group B and chronic nephritis group A.6.The positive expression rate of TLR4 had no correlation with blood urea nitrogen,serum creatinine,uric acid,HCO₃^-,cystatin C,retinol binding protein,white blood cell count,hemoglobin concentration,platelet count,monocytes,neutrophils,lymphocytes.7.The positive expression rate of TLR4 was positively correlated with the expression level of S100A8;The positive expression rate of TLR4 was not correlated with the expression level of S100A9.