Everolimus vs.Rapamycin for Treating Diabetic Nephropathy in Diabetic Mouse Model
10.1007/sl1596-011-0473-5
- Author:
CHENG LAN
1
;
CHEN JINGLI
;
MAO XIAOLU
Author Information
1. Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Keywords:
db/db mice;
diabetic nephropathy;
everolimus;
mammalian target of rapamycin;
mesangial cells
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2011;31(4):457-462
- CountryChina
- Language:Chinese
-
Abstract:
In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic (db/db) mice received everolimus (2 mg/kg every day) or rapamycin (2 mg/kg every day) for 4 weeks or 12 weeks respectively.Blood and 24-h urine samples were collected for biochemical tests.One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis.The expression levels of transforming growth factor-β1 (TGF-βl)and phospho-p70s6k were detected by using ELISA and Western blot,respectively in the renal 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,everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose.Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo,which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorptionrate.
