The Expression And Significance Of Thrombospondin-1 And Its Receptor Signal Regulatory Protein? In Focal Segmental Glomerulosclerosis With Acute Renal Tubular Interstitial Injury

Objective: To analyze the distribution and expression changes of thrombospondin-1(TSP-1)and its receptor signal regulatory protein?(SIRP?)in renal tissues of focal segmental glomerulosclerosis(FSGS)patients with acute tubular interstitial injury;to explore the correlation between the expression of TSP-1 in renal tubulointerstitium with the severity of tubular interstitial injury,clinical indexes,laboratory indexes and peritubular capillary(PTC)density;to study the changes of TSP-1 level in the patients' blood and urine.Methods: A total of 56 FSGS patients with acute tubular interstitial injury and15 paracancerous normal tissues were included.,the patients were divided into groups according to the severity of tubular interstitial injury,and the differences in clinical and laboratory indexes between patients with different severity of injury were compared.The changes in distribution of TSP-1,SIRP? and a marker of PTC endothelial cells CD34 in renal tissues were analyzed by immunohistochemical staining.Immunohistochemical staining results were scanned and quantified by digital pathological scanning system(Aperio),so as to obtain the expression quantity of TSP-1 and SIRP? in the renal tissues and the changes of PTC density.Analyze the correlation between the expression of TSP-1 in renal tubulointerstitium with the severity of tubular interstitial injury,clinical indexes,laboratory indexes and PTC density.According to the positive expression rate of TSP-1 in renal tubulointerstitium,FSGS patients with tubular interstitial injury were divided into the group with lowexpression of TSP-1(less than 10%)and the group with high expression of TSP-1(be equal or more than 10%),the differences in clinical indexes,laboratory indexes and PTC density between the two groups were analyzed by ANOVA.The level of TSP-1in serum and urine in normal controls and FSGS patients with acute tubular interstitial injury was detected by ELISA,and the differences were analyzed.Results: Among the 56 cases of FSGS patients with acute renal tubular interstitial injury,22 were in the mild group,18 were in the moderate group,and 16 were in the severe group.The age,urine NAG and serum creatinine(Scr)of the severe group were higher than that of the mild and moderate group,the albumin in the moderate group was lower than that in the mild and severe groups,the blood urea nitrogen(BUN)of mild group was lower than that of moderate and severe group,there was no significant difference in blood lipid,urine retinol binding protein(RBP)and urine protein quantitation between the three groups.The expression of TSP-1 in tubulointerstitium was significantly increased in FSGS with acute tubular interstitial injury,and mainly expressed in the epithelial cells of proximal renal tubules,but there was no significant difference in the expression of TSP-1 between the groups with different injury severity;the expression of its receptor SIRP? in tubulointerstitium did not change significantly,while decreased in glomerular podocytes;CD34 was mainly expressed in glomerular endothelial cells and interrenal peritubular capillary endothelial cells,PTC density did not change significantly compared with the normal control group.The expression of TSP-1 in renal tubulointerstitium was negatively correlated with urine RBP,urine protein quantitation and Scr,while no correlation with age,urine NAG,blood albumin,blood lipid,and PTC density.There were 20 cases in the low expression group and 36 cases in the high expression group.The urine protein quantitation(12.51(9.11-16.41)g/24 h vs 8.53(5.92-13.90)g/24h),Scr(1.96(1.19-3.43)mg/dl vs 1.5(1.03-1.94)mg/dl)and urine RBP(19.72±13.66mg/l vs 12.04±11.81mg/l)were significantly increased in the group with low TSP-1 expression compared with the group with high TSP-1 expression.There were no significant differences in age,blood lipid,urine NAG,albumin,BUN,and PTC density between the two groups.The serum and urine TSP-1 level in FSGS patientswith acute tubular interstitial injury were not significantly different from those in the control group.Conclusion: When FSGS was accompanied by acute tubular interstitial injury,the expression of TSP-1 in renal tubules was increased,and the positive rate of TSP-1expression was correlated with renal damage indexes.The expression of SIRP? in glomerulus was decreased.