Protective Effects And Mechanisms Of Sustained-release Of Dexamethasone In Safranine O-induced Nephritic Rabbits

Clinical manifestations of NS which is characterized by a large number of proteinuria,hypoalbuminemia,hyperlipidemia and edema,The primary NS is glomerular nephropathy which was happened with bilateral renal glomerulus and have different etiologies.Dexamethasone is one of the representative drugs of glucocorticoids,with powerful anti-inflammatory antivirus and allergy effect,estensive in clinical application,obvious inhibition HPA.Dexamethasone could inhibit renal inflammatory reaction and relieve symptoms.This treatment usually use intravenous injection,late oral dexamethasone therapy to maintainhe the resulting side effects,these side effects increase the patients pain in the process of treatment.So our vision for the treatment of nephritis which dosage forms could increase concentrations of medication in renal in the meantime reduce the whole body blood drug concentration.Whether this dosage form design can increase the curative effect,could reduce the side effects.In this reach we used the new dosage form called sustained-release of dexamethasone.SR Dex,a new long-term glucocorticoid implant preparation,which is characterized by sustained steady constant release,topical administration,rapid onset,long duration and so on.Animal model is safranine O-induced nephritis rabbits.Safranine O can selectively cause proximal and distal renal tubular epithelial cell necrosis,formation of nephritis model are consistent with clinical manifestations,with the clinical manifestations are consistent.Aim To study the protective effects of SR Dex in safranine O-induced nephritis rabbits,the impact on the HPA axis and adrenal functionthe.Possible mechanisms of glucocorticoid hormones drug for the treatment of nephritis.Methods Injected safranine O into rabbits?vein to built nephropathy model.Total dose 30 mg twice every three hours.Disposable injecting SR Dex(1.48,0.74,0.37mg/kg)by renal surgery.The positive treatment groups give dexamethasone(0.4mg/kg,qd×8d)by intragastric administration.To observe every groups rabbits general condition in everyday,test weight 24 h urine protein once a week.Test renal function incould total protein,albumin total cholesterol serum creatinine blood urea nitrogen uric acid and serum electrolytes(Na+,K+,Cl-)every two weeks.Test adrenal function incould adreno cortico tropic hormone corticosterone 17-hydroxy-cortico-steroid every two weeks.HE observed in renal and adreno pathological changes,PAS observed in glomerular mesangum and glomerular basement membrane morphological changes,SR observed renal tissue collagen fibers IHC method to detected the expression of nephrin and TRPC6.Real-time PCR method to detected m RNA of nephrin and TRPC6.Results SR Dex treatment groups protective effect in the safranine O-induced nephritic rabbits in two aspects Reduce 24 h urine protein,urine specific gravity,serum creatinine,blood urea nitrogen,uric acid,total cholesterol,increase total protein,albumin,improve the renal and adrenal histopathological changes.Conclusion These results suggest that SR Dex could improve safranine O-induced nephritis rabbits.The underlying mechanism might be inhibite the down-regulation of nephrin associated decreased the expression of TRPC6,to improve the integrity of glomerular filtration membrane.In addition SR Dex has no obvious inhibition to HPA and no obvious influence to adrenal form and function.