The Expression And Intervention Of Matrix Metalloproteinase And Tissue Inhibitor Of Metalloproteinase In Remnant Kidney Rats

Objective: To investigate the distribution, expression and variation of MMP-2,9 and TIMP-1 in remnant renal tissues of 5/6 Nephrectomy young rats,and to evaluate the interfering effects of angiotensin converting enzyme inhibitor (ACEI) combined with angiotensin receptor agonist (ARB). So we may be to get some new clues and evidences for understanding the patho- genesy and finding the treatment on chronic renal failure in children.Methods: 5/6 Nephrectomy remnant young rats used as a classical chronic renal failure model. When the models were succeed,those 72 Wistar female young rats were divided randomly into three groups. That was 5/6NX untreated group, 5/6NX treated by ACEI combined with ARB and sham group. At different time points of treated for 2,4,8,12 weeks, we measured proteinuria in 24 hours of rats,blood urea nitrogen,serum creatinine,cholesterol ,triglyeride and detected the protein distribution and expression of MMP-2,MMP-9,TIMP-1 in remnant renal tissues by the way of immunohistochemical technique. Meanwhile, we also evaluated the changes of this protein expression and visited the interfering effects of treatment with Lotensin and Cozaar.Results: The urine protein for 24 hours, cholesterol, triglyeride were increased progressively,the Bun, Scr etc. were deteriorated progressively in 5/6NX untreated group rats, and chronic kidney failure were presented in the untreated group of 5/6 Nephrectomy young rats. But in each treated group, these changes were ameliorated (P<0.05). At all time points in experiment, the proteinuria and each serum biochemical parameters reflecting renal function are no difference in sham group rats (P>0.05). The renal pathological results by HE staining had showed that focal inflammatory cells infiltrated into renal tissues at 2th week, mesangial proliferated lightly,pile monocyts/moscrophages infiltrated into tubulointerstitial regions,The tubule epithelial cells swelled, proteinuria casts in tubule were observed at 4th week. With prolongation in experiment time ,these pathological changes aggravate gradually. At 12th week had showed that glomerular capillaries were collapsed, mesangial proliferated and its matrix to broad, tubule were dilatalted or atrophied widespread, heavy proteinuria casts presented in tubular cavities, the mass fibrin accumulated in tubulointerstitial. But those pathological changes were ameliorated significantly in treated groups. Through immunohistochemical staining and semiquantitative analysis of immunohistochemical positive signal, we had detected that the...