The Study Of Shenshuning Of Smoothing Shaoyang And Treating Both The Primary And Secondary Aspects Therapy On Glomerulosclerosis Rats And Its Mechanism

PURPOSE: Glomerulosclerosis is the morphological expression of end-stage nephrology, except for renal transplantation, the deposition of extracellular matrix and growth factor are the important factors for its happening and developing. In this study, we evaluated pathology, cytoplasmic factor and the phenotypic transition of primary kidney cells in the glomerulosclerosis rats, to explore the mechanism of the glomerulasclerosis and the effects of Shenshuning of smoothing shaoyang and treating both the primary and secondary aspects therapy on glomerulersclerosis rats and its mechanism.METHODS: We used glomerulosclerosis rats model induced by unilateral nephrectomy(Nx) and injecting Doxorubicin Hydrochloride,dynamicly excemined the weight,24hour proteinuria,plasma albumin, total serum protein and the renal function; At the end of 8 weeks, we observed the renal morphological expression and ultrastructure;performed immunohistochemical staining to explore the extracellular matrix of the renal tissue as collegenIV,fibronection,laminin and transforming growth factor ?i,a-smooth muscle actin. Used reverse transcription-polymerase chain reaction (RT-PCR) to mensurate the gene expression of plasminogen activator inhibitor -1, tissue inhibitor matrix metalloproteinase-1, transforming growth factor-Pi and hypetacyte growth factor.RESULTS: l.The gomerulosclerosis rat's model is succeeding: The glomerulosclerosis model rats growths slowly. At the end of 8weeks,the model rats show more proteinuria,low plasma albumin and total serum protein,almost all of the lipid was up regulated and the renal function was lowing(P<0.01);the extracellular matrix as collegenIV,fibronection,laminin was depositing(P<0.01).The renal tissue morphologic show prominent proliferation of mesangial cells and matrix,about 80% glomeruli have segmental glomerulosclerosis,amonst 25%-50% show diffuse sclerosis; the renal epithelial cells necrosis, tubular atrophy and interstitial fibrosis. Electron microscopic examination of glomeruli showed enhanced cellular proliferation, revealed ultrastructural features consistent with focal segmental glomerulosclerosis: an increase in mesangial matrix, effacement of foot processes, and thickening of basementmembrane. Interstitial fibrosis subsequently developed. This findings demonstrated that the succeed of the glomerulosclerosis rats model.2.The effects of shenshuning on glomerulosclerosis rats.Shenshuning and benazepril can decreased protienuria and high lipid ,protected renal function of the model rats,and shenshuning can notably decreased plasma cholesterol and creatinine,but not find more effects on plasma albumin and total serum protein(P>0.05).Light microscopic show shenshuning can protect and repaired the glomeruli capillary network,renal cells,renal epithelia cells and interstitial tissule.Benazepril can protect the glomeruli while show no more function for the epithelia cells and interstitial tissue.The immunohistochemical staining expored collagen IV mainly expressed at glomerulus basement membrane,around capillary, mesangial matrix and sclerosis area,basement membrane of epithelial cells and interstitial fibrosis area;Laminin is mainly expressing at glomeruli mesangial matrix, cytokines,basement membrane,the epithelial cells of outstretched renal tubular and interstitial fibrosis area;Laminin mainly expressed at the basement membrane of the glomaruli and tubular epithelial cells,interstitial fibrosis area.The expression of collagen IV,fibronectin and liminin is low in normal group,while the expression is high in glomerulosclerosis group.Shenshuning and benazepril treatment attenuated them expression, and the functions are similar of the two medicines. While shenshuning show advantages than benazepril at depressing fibronectin and collagenlV.Transforming growth factor-Pi is mailly distributing at the glomerula cells cytokiries,massengil matrix and tubular cells cytokines and the sclerosis area.Normal group rat renal tissue shows faintness expression,the glomerulosclerosis rats show high expression,so...