The Correlation Between Disorders Of Throm-fibrinolysis System Mediated By Thrombospondin-1(TSP-1) With Tubulointerstitial Fibrosis In Remnant Renal Tissues Of 5/6 Nephrectomy Young Rats

Objective: To investigate the effects of thrombospondin-l(TSP-1) expression on the throm-fibrinolysis system during progressive chronic renal lesions or tubulointerstitial fibrosis in remnant renal tissues of 5/6 Nephrectomy young rats,and to evaluate the correlation between of them, and to study the interfering effects of treated with angiotensin converting enzyme inhibitor(ACEI) Benazepril and Hirudo.Methods: 5/6 Nephrectomy remnant young rats used as a classical chronic renal failure model. When the models were succeed that through evaluated the proteinuria, blood pressure, serum bichemical parameters and renal pathological changes. Then, those model animals were divided randomly into five groups. That was 5/6NX untreated group; 5/6NX treated with Hirudo; 5/6NX treated with ACEI; 5/6NX treated by ACEI combined with Hirudo and sham group. At begin in the experiment, 4th week, 8th week, and 12th week, we measured the body weight, blood pressure and proteinuria in 24 hours of rats, and detected the protein expression of TSP-1,PAI-1, TGF-El uPA and tPA in remnant renal tissues by the way of immunohistochemical technique. These protein expressing changes and relativity of them were evaluated and to analysis the pathogenic role of these parameters changes in renal lesions, and to visit the interfering effects of treatment with angiotensin converting enzyme inhibitor(ACEI) Benazepril and thrombin inhibitor-Hirudo.Results: The renal failure was observed progressively after model young rats undergoing 5/6 Nephrectomy in untreated group. At the 12th week followed treatment, the body weight of rats were lose step by step, and blood pressure,urinary protein were increased progressively. At all time points in experiment, each serum bichemical parameters reflecting renal function are normality in sham group rats. However, the BUN, Scr etc. were deteriorated progressively in 5/6NX untreated group rats, and their plasm total protein and albumin were decreased progressively. The hyperlipemia and chronic kidney failure were presented in those model rats. But in each treated group, these changes were ameliorated following treated with Hirudo and ACEI or combined with two medicines. This treated effect was more excellent in combining treated group than in others. The urinary total plasminogen activators(PAs) activity in 5/6NX rats that untreated was descented than sham rats. And the PAs largest activity in 24 hours'urine was observed at 8th week after the treatment. In each treated groups, urinary PAs was decreased following treatment continuily, renal function was recovered, and proteinuria was reduced. There are an relativity of PA with proteinuria in treated groups but no in untreated. The renal pathological results by HE staining at 12th week had showed that mesangial proliferated and its matrix to broad, the mass fibrin accumulated in Borman's capsule, glomerular capillaries were collapsed, tubule were dilatalted or atrophied widespreadly, heavy proteinuria casts presented in tubular cavities, pile monocyts/mocrophages infiltrated into interstitial and tubulointerstitial fibrosis developed. But those pathological changes was ameliorated significantly in treated groups. Through immunohistochemical staining, and semiquantitative analysis of immunohistochemical positive signal, we had detected that the protein expression of tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) in remnant renal tissue were downregulated generally ,and plasminogen activator inhibitor (PAI-1) , thrombospondin-l(TSP-l) and TGF-E1 expression were increased in 5/6NX untreated than in sham group, otherwise, tPA and uPA expression were enhanced in each treated groups, and PAI-1 ,TSP-1 and TGF-E1 was decreased markedly at same time. Especially, the interventive effects more significant in ACEIcombined with Hirudo'group than others. We had observed a positive correlation between TSP-land TGF-E1, PAI-1 expression on a time and location dependent pattern, and a negative correlation between TSP-1 and uPA, tPA prese...