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The emergence of the background and purpose of microalbuminuria means the arrival of diabetic nephropathy (DN) in patients with diabetes, proteinuria not only clinical manifestations of DN is to accelerate the progress of the main reasons. By porous endothelial cells, the glomerular basement membrane (GBM) and podocyte its adjacent foot the sudden hiatus between the diaphragm common form of glomerular filtration membrane mechanical and charge barrier in the formation of proteinuria plays important role. Heparan sulfate proteoglycans (HSPGs) is a glycosaminoglycan constitute GBM and mesangial extracellular matrix (ECM) of biological macromolecules the heparanase (Heparanase, HPA) is a can Degradation of the HSPGs side chains of heparan sulfate HS endogenous β-glucuronic acid, the enzyme, thereby changing the charge barrier so that the damage to the filtration function HSPGs in GBM and ECM expression distribution, destruction of GBM. Pathogenesis of DN, in addition to recognized the high-fat high-sugar, high-glomerular hemodynamics, renin - activation of the renin-angiotensin system, the intensification of oxygen free radical damage and nonenzymatic role influencing factors, In recent years, some scholars have found that detected in DN patients microalbuminuria urine accompanied by the emergence of the HPA, HS, further study found that, in the kidney tissue of patients with GBM DN HPA high expression accompanied by a basement membrane HS the staining decreased the formation of kidney tissue protein HPA expression of DN proteinuria, become a research hotspot in recent years. This experiment created by streptozotocin (STZ) DN rat model to observe the HPA, b-FGF and further explore the mechanism of proteinuria in the tissues of STZ nephropathy, and with special intervention Shuluo ground, through biochemical , reverse transcriptase polymerase chain reaction, immunohistochemistry detection methods, and thus to clarify the mechanism of Shuluo detemir in to reduce the DN proteinuria clinical application of its theoretical basis. Method 4-week-old male SD rats 70 the adaptive feeding for a week, were randomly divided into a control group (n = 20) and DN group (n = 50). DN group, one-off to give 0.1 mmol / L concentration of streptozotocin preparation the liquid (STZ60mg/kg) by intraperitoneal injection for three consecutive days after the 72 hours testing blood glucose, blood glucose greater than 16.6mmol / L, 24h urine output greater than the control group urine 1.5 times the amount of the successful modeling. Control group, intraperitoneal injection of streptozotocin buffer. After the success of the model, DN treatment group be Shuluo detemir (10mg/kg.d) by intraperitoneal injection of 8 weeks; control group, model group the isodose saline intraperitoneal injection of 8 weeks. During the experiment, the animals free food and water, not the use of insulin and other hypoglycemic agents. 4 weeks and 8 weeks, 10 rats in each group were sacrificed. Determination of 24h urine protein and blood biochemical indicators; take the kidney, renal histopathologic examination, using reverse transcriptase polymerase chain reaction, immunohistochemistry to detect HPA expression in the kidney tissue; immunohistochemistry to detect b-FGF in kidney tissue expression. Results 1 model group, treatment group 24h urinary protein excretion in 4 weeks and 8 weeks compared with the control group was significantly higher (P lt; 0.05), urinary protein excretion of the treatment group compared with the model group was significantly lower (P lt; 0.05) ; model group, serum albumin level in 4 weeks and 8 weeks than those in the control group, the treatment group was significantly decreased (P lt; 0.05), serum albumin level in the treatment group compared with the control group, 4 weeks and 8 weeks, no statistical difference Significance: model group, the proportion of treated rats renal (kidney weight / body weight) than the control group was significantly higher (P lt; 0.05), the proportion of treated rats kidney compared with the model group was significantly lower (P lt; 0.05); model Cys-C level of the blood of rats compared with the treatment group and the control group was significantly higher (P lt; 0.05), the level of serum Cys-C treatment group compared with the control group, the difference was not statistically significant. 2. Pathological changes in the kidneys of rats: control group renal histopathology roughly normal; 4 weekend, model group, renal proportion of glomerular volume increased significantly, increased extracellular matrix and basement membrane thickening, extending to 8 weeks appear glomerulosclerosis, renal interstitial fibrosis; treatment group compared with the model group, pathological changes of the kidney tissue was significantly reduced. Reverse transcription-polymerase chain reaction results showed: HPA mRNA weak expression of rat kidneys in the control group, the model group, higher expression in 4 weeks and continue until 8 weeks, the treatment group 4,8 weekend HPA mRNA expression model group was significantly lower. Immunohistochemical results: the control group, HPA, b-FGF expression in glomerular and tubular interstitial have weak model group 4 weekend HPA, b-FGF expression in the kidney tissue was significantly higher, and has been extended to 8 weeks; treatment group HPA, b-FGF in renal tissue compared with the model group decreased significantly (P lt; 0.05). With streptozotocin DN progress rat glomerular tubular interstitial HPA, b-FGF expression significantly increased, suggesting that the expression of HPA, b-FGF may be elevated streptozotocin DN the DN rats urine protein was significantly reduced after the intervention of the important factor in rat urine protein 2. Shuluo detemir, its mechanism of action may be related to the lowered renal tissue expression of b-FGF.
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