Everolimus Is More Effective Than Rapamycin In Treating Diabetic Nephropathy In A Diabetic Mouse Model

Objective:To research the protective effect of everolimus on high glucose induced the apoptosis of mesangial cells and discuss the significance. Methods:We collected and divided HBZY-1 cells. After treating cells with agent for 72h, we detected OD values with SRB method to calculate the cells growth rate and detected apoptosis cells rate with flow cytometry. Results:The growth rate of mesangial cells treated with 30mM glucose was significantly decreased and the apoptosis rate was significantly increased (P＜0.05). The different concentrations of everolimus might raise the growth rate of cells (P<0.05), in which the effect of 200ng/ml everolimus was the best (P<0.05). Meanwhile,200ng/ml everolimus could significantly prevent the apoptosis of cells. Conclusion:Everolimus could prevent high glucose induced the apoptosis of mesangial cells, so there is a new method for the treatment of diabetic nephropathy.Part two Effect of everolimus on kidney disease of db/db miceObjective To research the effect of everolimus on kidney in diabetic rodent model. Methods twelve db/m mice and twelve db/db mice were divided into four groups. Each group contained six mice as follows:db/m mice, db/m mice with everolimus treatment, db/db mice, db/db mice with everolimus treatment. Mice with treatment received everolimus 2mg·kg-1·day-1 for 8 weeks. At the end of experiment, blood samples were withdrawn for biochemical analysis. kidneys from each mouse were used for histological analysis Results blood urea nitrogen, plasma creatinine, glomeruli area and kidney weight of db/db mice without everolimus were overt increased and their glomerular extracellular matrix was excessive accumulation. These results were prevented by everolimus. Conclusion Everolimus prevent the progression of diabetic nephropathy. Our study presented a new drug to treat diabetic nephropathyPart three Everolimus is more effective than rapamycin in treating diabetic nephropathy in a diabetic mouse modelSummary:Our aim was to evaluate the effectiveness of everolimus compared to rapamycin in the treatment of diabetic nephropathy. Eight-week old diabetic (db/db) mice received everolimus 2mg/kg/day or rapamycin 2mg/kg/day for 4wks or 12wks. Blood and 24 h urine samples were collected for biochemistry. One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis. The expressions of transforming growth factor-β1 and phospho-p70S6 kinase were examined using ELISA and Western blot, respectively in kidney tissue as well as in mesengial cell culture samples. Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy, and in decreasing accumulation and expansion of the extracellular matrix. However, the effect of everolimus on inhibiting the mammalian target of rapamycin pathway in vitro was less than rapamycin at the same dose. Everolimus was more effective compared to rapamycin in preventing diabetic nephropathy in vivo. One possible reason may be that everolimus has better bioavailability and a higher oral absorption rate.