The Relation Between Vascular Interrelated Factors' Changes And Renal Interstitial Fibrosis In IgA Nephropathy

Objective: The IgA nephropathy is the most common type in nephritis in our country. 20%~40% patients gradually develop into ESRD in the latter 5~25 years. Not only the glomerular sclerosis, the renal function damage, hypertension and the urine protein are related with the IgAN, but also the interstitial fibrosis is close with the prognosis. The lost of peritubular capillaries can influence the blood, oxygen and nutrient's supply in the kidney interstitial substance. thrombospondin-1(TSP-1) is a extracellular matrix glycoprotein, it could bind to CD36, and then inhibit Bcl-2's expression,increase Bax's expression. In this way, apoptosis of the endothelial cells can be induced, and angiogenesis can be inhibited. Vascular endothelial growth factor (VEGF) is a high degree of specificity mitogen of the endothelial. We observed the expression of the TSP-1, TSP-1mRNA, and VEGF in IgAN nephropathy tissue; elucidate the influences on peritubular capillaries and the role they play in IgA nephropathy interstitial fibrosis.Methods: Fifty-four patients (male twenty-eight samples, female twenty-six samples,age32.31±12.65years) in department of nephrology of the second hospital of Hebei Medical University were involved. All patients were diagnosed as primary IgAN by renal biopsy evaluated by light microscopy,immunofluorescence and electron microscopy. All patients had excluded Henoch Schonlein purpura nephritis, nephritis associated with hepatitis B, lupus nephritis, hepatic sclerised glomerulosclerosis and so on. All patients did not use glucocorticosteroid, immunodepressant and Low Molecular Heparin before renal biopsy. the clinical dates were be collected, include blood pressure, serum chol, plasma albumin, serum iga, urine protein quantization, urine osmotic pressure, serum creatinine, and so on. The invalid renal tissue were classified by Katafuchi scale into four groups, including GroupⅠ-Ⅳ(Ⅰgroup: nine samples,Ⅱgroup: seventeen samples,Ⅲgroup: fifteen samples,Ⅳgroup: thirteen samples).ten patients with MCD were negative control group. The expression of TSP-1,VEGF,Col III,CD34 were detected by immunohistochmistry; The expression of TSP-1 m RNA was detected by hybridization histochemistry. We counted the quantity of the capillaries that signed by CD34 from the microscope, and made the average value be the peritubular capillary index (PCI).Results: 1.capillary endothelial was signed by CD34 to observe the peritubular capillaries. In control,ⅠandⅡgroups, capillaries stretched well. Among those groups, the difference of PCI has no statistically significant(27.0±1.88～ 22.9±3.89,P=0.328～0.311);But in theⅢ,Ⅳgroups ,the capillaries'lumen deflated gradually,the PCI was decreased (22.9±3.89～14.56±2.28 P <0.05)2. The expression of TSP-1 and TSP-1 mRNA in nephridial tissue: In control andⅠgroups, renal tissues show no expression of TSP-1 and TSP-1 mRNA in nephridial tissue. With the progress of pathological change in IgA nephropathy, the expression of TSP-1 was increased from I to IV groups(TSP-1 increased from 3.11±1.50% to 33.97±9.18%,P<0.01 ; TSP-1m RNA increased from 17.64±1.21 % to 37.03±9.63 %, P<0.05 ) . The expression of TSP-1 and TSP-1mRNA were mainly located in endochylema of renal tubular epithelial cell and no expression in glomeruli.3. The expression of VEGF and collagenⅢ: renal tissues show lepto-expression of VEGF in glomeruli, and hypos-expression in endochylema of renal tubular epithelial cell. the difference between control groups and I groups didn't have statistically significant(P=0.396). The expression of VEGF in groupⅡwas stronger than the normal control groups;in groupⅢ,the expression has a significant increase(from 1.48±7.54% to 40.20±5.47%,P<0.05) .but in group IV, it's decreased ( from 40.20±5.47 % to 19.53±5.45%,P<0.01).collagenⅢwas mainly located in Glomerular mesangium interstitial substance,renal interstitial. With the progress of pathological change in IgA nephropathy, the scope and intensity which the collagenⅢexpressed gradually increased. the rate of glomerular sclerosis increase gradually(from 0.43±1.00 % to 48.52±32.61 % ),and the interclass differences had statistical significance(P<0.01).it had positive correlation with interstitial fibrosis and collagenⅢ(r=0.546,P<0.01).4.The expression of TSP-1 and TSP-1 mRNA had positive correlation with The expression of collagenⅢ(r=0.671,0.655,P <0.05), and they had inverse correlation with PCI(r=-0.644,-0.564,P <0.05)。But TSP-1 and TSP-1mRNA had no correlation with The expression of VEGF(r=-0.324,-0.375,P=0.28～0.14 ) .The expression of TSP-1 and TSP-1mRNA had positive correlation with,the rate of glomerular sclerosis and urine protein, and had no correlation with age,sex,serum iga,plasma albumin,serum chol,urine osmotic pressure,,blood pressure and the course of disease。Conclusion: The interstitial fibrosis of IgA nephropathy has plenty of relationship with peritubular capillaries'reduction. the alter of vascular interrelated factors could lead to peritubular capillaries'change,and then promote the progress of IgA nephropathy。The expression of VEGF increased when the early IgA nephropathy,but this increase couldn't continue.in theⅠ,Ⅱgroups,VEGF show a brief protection to capillary endothelium in renal interstitium.The increase of TSP-1 may lead to the peritubular capillaries'decrease, and aggravate renal interstitial fibrosis.