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ObjectiveThe aim of this study was to observe the protective role of sodium ferulate onkidney of diabetic nephropathy rat and explor the influence on the expression ofsmad1,smad7,transforming growth factor-β1(TGF-β1) and typeⅣ collagen(Col Ⅳ) to investigate the prossible prevention mechanism of sodium ferulate ondiabetic nephropathy.Methods10healthy male Sprague-Dawley rats which were allocated randomly wereassigned to normal control group(NC group).while the remaining40malediabetic model rats which induced by the single injection of streptozotocin (STZ)via coccygeal vein were randomly divided into untreated-diabetic group(DMgroup),and sodium ferulate low-dose, middle-dose and high-dose treatmentgroup (SL,SM,SH group),each containing10rats.Rats in SL,SM and SH groupwere treated respectively with sodium ferulate at doses of50,100and200mg·kg-1·d-1by gavage administration, while NC and DM group rats were treatedwith corresponding sodium chloride.The Urinary albumin excretion rate(UAER)and Fasting blood glucose(FBG) were tested at the second,fourth and eighthweekend.After8weeks of STZ induction,Serum creatinine(Scr),Blood ureanitrogen(BUN) were examined.The morphologicai changes of renal cortex wereassessed through Hematoxylin-Eosin staining method and through glycogenstaining to know the content of glycogen in cells by light microscope.Theultrastructure was observed by electron microscope.The expressions of smad1,smad7,TGF-β1and ColⅣ on nephridial tissue were evaluated by bothimmunohistochemistry and western blotting.ResultsAt the end of the study period,the levels of weight of DM,SL,SM and SHgroup were declined statisically significant when compared to the NC group,while the levels of kidney weight/body weight were increased significantly whencompared to the NC group.The levels of weight of SL,SM and SH group wereincreased significantly when compared to the DM group,while the levels ofkidney weight/body weight were opposite.There were statistical significanceamong the group SL,SM and SH,but SH group changed most significantly.UAER,FBG:The levels of UAER were increasing during the disease course.At the end of the fourth and eighth week,DM,SL,SM and SH group hadsignificantly higher UAER and FBG when compared to NC group,while theywere lower in SL,SM and SH group when compared to DM group.Howeverthere was no significant difference at second week. Significant differences werefound among the SL,SM and SH group.SH group changed most significantly.Serum biochemical values:The levels of serum creatinine(Scr) and bloodurea nitrogen(BUN) were increased significantly in DM,SL,SM and SH groupwhen compared to NC group,while the levels of those were decreased signific-antly in SL,SM and SH group when compared to NC group.They had statisticalsignificance among SL,SM and SH group.SH group was more significantly.Light microscope:Hematoxylin-Eosin staining:Compared to NC group,DM,SL,SM and SH group were characterized by the volume of glomerular capsulesincreasing,the glomerular capsules wall thickening,part of them accretived,glomerular endothelial cells proliferation and mesangial matrix expansion,capillary net lobulated and renal tubular epithelial cell swolling.when comparedto DM group, SL,SM and SH group were improved significantly and SH groupwas most remarkable.Glycogen staining:Glycogen particles was mainly located in epithelium of proximal tubules in DM,SL,SM and SH group,when compared toNC group.Glycogen decreased obviously in SL,SM and SH group whencompared to DM group.SH group changed most significantly.Electron microscope: DM,SL,SM and SH group were characterized by theglomerular basement membrane thickening,some of them uneven,the mesan-gial matrix region expanding and adjacent foot process fusion or broken,whencompared to NC group.Ultrastructure changes in SL,SM and SH group wereimproved significantly by electron microscope when compared to DM group,SHgroup most significantly.The expression of proteins by immunohistochemistry and western blotmethod:The expression of smad1,TGF-β1and ColⅣwere increased significantlyin group DM,SL,SM and SH (p<0.05),when comparing to NC group.While SL,SM and SH group were declined (p<0.05),when comparing to DM group.Smad7was opposite(p<0.05).There were significant differences among SL,SM,SHgroup(p<0.05),SH group changed most significantly.Conclusion1The kidney ultrastructure and renal function of diabetic rats had changedaffter8weeks of STZ induction.2Sodium ferulate could improve the renal ultramicrostructure and renalfunction.3Sodium ferulate had a protective role to diabetic nephropathy,themechanism might be related to improving glycometabolism,reducing theexpression of smad1,TGF-β1and ColⅣ and increasing Smad7in kidney tissue.4The kidney protective effects of sodium ferulate on diabetic rats was found adose-response relationship.
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