Protective Effects And Mechanisms Of Dexamethasone Implants Through Renal Capsule Injection In Adriamycin-induced Nephritic Rats

Nephrotic syndrome, which is characterized by a large number of proteinuria, hypoalbuminemia, hyperlipidemia and edema, ultimately can lead to renal failure. Adriamycin-induced nephropathy is a kind of classic simulate human chronic kidney disease animal model, which has been widely used in the field of kidney disease. Proteinuria,which is the most representative clinical manifestations of kidney disease, not only one of the signs of kidney damage, but also as a risk factor involved in a variety of progression of kidney disease. Glucocorticoids, which is one of the clinical treatment of nephrotic syndrome commonly used drugs, the classic method of treatment is the use of high-dose oral or intravenous injection, but inevitably, easy for patients to bring a series of side effects, such as infections, ulcers, osteoporosis and so on, seriously restore the large-scale use of the drug. Dexamethasone implants, a new long-term glucocorticoid implant preparation, which is characterized by sustained steady constant release, topical administration, rapid onset, long duration and so on. Our research focuses on exploring the protective effects of dexamethasone implants and its potential mechanisms in adriamycin-induced nephritic rats.Aim To study the protective effects and mechanisms of dexamethasone implants in adriamycin-induced nephritic rats.Methods The adriamycin-induced nephropathy model was built by injecting adriamycin (7.5mg/kg) into tail-vein twice every two weeks in SD rats. The dexamethasone implants treatment groups (2.8,1.4,0.7mg/kg) was made by surgery in the kidney capsule disposable injection and positive drug dexamethasone treatment groups (0.1 mg/kg, qd×8w)was made by intragastric administration. Every day at different time during the experiment to observe and detect rat general condition, weight,24h urine protein, urine specific gravity, blood biochemistry and so on, blood indicators, which is included renal function (serum creatinine, blood urea nitrogen), protein (total protein, albumin), lipids (total cholesterol), uric acid, and serum electrolytes (Na+, K+, Cl"). After the end of the experiment, renal tissue taken part in 4% paraformaldehyde, the rest in-80℃. Hematoxylin and eosin (HE) observed in renal pathological changes, rat kidneys are stained with periodic acid-Schiff for observed the morphological changes of mesangial and basement, rat kidneys are stained with sirius red for observed the renal tissue collagen fibers; expression of Nephrin, podocin and CD2AP were detected by immunohistochemistry (IHC); expression of Nephrin was examined by western blotting (WB).Results Different dose of dexamethasone implants could significantly improve the adriamycin-induced nephritic rats in general condition, reduce 24h urine protein, increase renal function (serum creatinine, urea nitrogen), elevate serum protein (total protein, albumin),lower blood lipids (total cholesterol), improve the histopathological changes, decreased the expression of Nephrin and CD2AP but inhibite the down-regulation of podocin in protein levels on the renal cortex of the ADR rats.Conclusion These results suggest that dexamethasone implants could have better protective effect in adriamycin-induced nephritic rats. The underlying mechanism might be associated with the restoration of the expression of Nephrin, Podocin and CD2AP on podocyte slit diaphragm.