| Background:Diabetic nephropathy (DN) is the major cause to end-stage renal failure (ESRD).Recently，the incidence of diabetes in developing countries (including China) is rapidlyincreasing. So it is can be predicted in the near future, DN will also become the main reasonof ESRD for Chinese. The main pathological lesion of diabetic nephropathy is glomerularbasement membrane thickening and extracellular matrix accumulation. In the early of DN,glomerular filtration rate increased is the mainly change demonstrating increased blood flowin the kidney. The increased glomerular size, thickened glomerular basement membrane andincreased extracellular matrix were the main demonstration in Pathology. As the lesionprogressing，the kidney function will gradually injured, and when the clinical manifestationsappear (urinary protein over200μ g/min)，it is hard to correct and improve the prognosis. Arecent study shows that, GSK-3β in liver and muscle tissue was abnormally activityincreased in the type2diabetes. It weakened the conduction of insulin signals, inhibited theuse of the sugar and glycogen synthesis process, and then insulin resistance appeared.Therefore, it becomes more important in the treatment of diabetes to explore the etiology andpathogenesis of type2diabetes.Objective: To analysis the function of GSK-3β and GSK-3β inhibitor in insulin signalpathway by the rat model of diabetic nephropathy，we can study the effect of GSK-3β onextracellular matrix accumulation in diabetic nephropathy. Also it can afford the theory ofpreventive and treatment in diabetic nephropathy. It can supply the theory of the newmedicine and the research in diabetic nephropathy.Methods: Male Wistar rats were randomly divided into four groups: normal group (NCgroup, n=5), diabetic nephropathy (DN group，n=10), treatment group (DY group, n=20), inhibitor group (Y group, n=5). The rats were feed with high fat foods except for theNC to induce rats hyperinsulinemia and insulin resistance. The rat model of diabeticnephropathy was established by single intraperitoneal injection of STZ (35mg/kg). Before24hours of the rats were killed, we collected24-hour urinary protein. The heart blood wascollected before execution and kidney tissues were collected after sacrifice. Renal pathological changes were detected by microscope and fibronectin and laminin weredetected by immunohistochemical method.Results: The rat models of diabetic nephropathy and treatment models by singleinhibitor were successfully constructed. The general conditions consistented with respectivemodel, including body weight, kidney weight/body weight, urine protein and blood glucose.The kidney of DN rats showed increased glomerular volume, diffuse mesangial areawidened, extracellular matrix diffuse increased, part of the visible capillary basementmembrane thickened and capillary cavity occluded. Immunohistochemical results showedthat the expression of LN and FN was in the mesangial area. Compared with the normalcontrol group, the expression of FN and LN was no differenced in Y group, increasedsignificantly in DN group, and was no changes in DY group after treatment.Conclusion:1. Animal model of diabetic nephropathy was successfully achieved by highfat diets combined with small dose STZ. The diabetic nephropathy model by this way mayprovide a new method and tool to the study of the pathogenesis and the prevention of type2diabetes.2. Compared with the NC group, the24-hour urinary protein quantitative increasedsignificantly in DN group，and declined in the DY group. That will provide a broadapplication prospect for the new drugs of the diabetic nephropathy.3. The detection ofGSK-3β was important to the research of diabetes nephropathy. LN and FN expressed a littlein the NC group, significantly increased in DN group, no significantly changed in DY groupafter treatment. |
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