The Study Of The Renal Protective Effect And Mechanism Of Guijianyu In The Rats With Glomerular Sclerosis

PURPOSE:Glomerulosclerosis is the morphological expression of primary and secondary end-stage nephrology. The resent researches show deposition of extracellular matrix is one important factor of its happening, including its regulators. In this study, We used glomerulosclerosis rats model induced by unilateral nephrectomy(Nx) and injecting Doxorubicin Hydrochloride, to explore the mechanism of the glomerulasclerosis and the effects of Guijianyu on extracellular matrix metabolism and the correlative factors of glomerulersclerosis and its mechanism. METHOD:We used Sprague-Dawley glomerulosclerosis rats model induced by unilateral nephrectomy(Nx) and injecting Doxorubicin Hydrochloride after one week, treated with Guijianyu and Benazepril at the same time, examined the weight, 24hour proteinuria, blood creatinine and urea nitrogen, plasma albumin, total serum protein, cholesterol, triglyceride, low density lipoprotein and observed the renal morphological expression and ultrastructure; performed immunohistochemical staining to explore the extracellular matrix of the renal tissue as collegenlV, fibronection, laminin; reverse transcription-polymerase chain reaction (RT-PCR) to measure the gene expression of plasminogen activator inhibitor-1, tissue inhibitor matrix metalloproteinase-1, transforming growth factor-Pi, analyzing with HPIAS-20QO image analysis system. RESULT:1. Biochemical results show Guijianyu can decreased 24h protienuria, cholesterol, triglyceride, low density lipoprotein (PO.01), the function is similar with benazepril.2. The analysis of extracellular matrix deposition, glomeruli capillary diameters and glomerulosclerosis index show significant differentiation compare normal group with model group(PO.Ol), and the significant differentiation between Guijianyu group, benazepril group and model group(PO.Ol), and no more differentiation between the two treated groups(P>0.05).3. The immunohistochemical staining results show the expression of collagen IV, Laminin and fibronectin of model group rats are higher than normal group(PO.Ol), while the expression is low after treated with Guijianyu and benazepril. (P<0.01), there is no differentiation between the two treated groups(P>0.05).4. Reverse transcription-polymerase chain reaction(RT-PCR) results show the gene expression of transforming grows factor P i, plasminogen activator inhibitor -1 and tissue inhibitor matrix metalloproteinase-1 are high in the glomerulosclerosis rats tissue(P<0.01), Guijianyu and benazepril can down-regulated PAI-1, TIMP-1 and TCP-Pi mRNA gene expression(P<0.01), there is no differentiation between the two treated groups(P>0.05).CONCLUSION:1. Guijianyu is efficient strategy for treating glomerulosclerosis with decreased the proteinuria, hyperlipemia and protect renal function of the glomerulosclerosis rats.2. Guijianyu can depressed extracellular deposition such as collagen IV, Laminin and fibronectin, and attenuated the regulated system expression as TCP-Pi, PAI-1, TIMP-1 mRNA gene expression to preventing and treating glomerulosclerosis.