Mycophenolate mofetil and FK506 have different effects on kidney allograft fibrosis in rats that underwent chronic allograft nephropathy

摘要

Background Tacrolimus (FK506) is associated with renal fibrosis in long-term use. Mycophenolatemofetil (MMF) can also inhibit or attenuate the progression of renal fibrosis. This study aimed to determine the different effects of FK506 and MMF on fibrosis-associated genes in the kidney in rats that underwent chronic allograft nephropathy (CAN). Methods Fisher (F344) kidneys were orthotopically transplanted into Lewis rat recipients. All recipients were given Cyclosporin A (CsA) 10?mg/kg-1.d-1?×?10?day and were then randomly divided into three oral treatment groups (n?=?9 in each group): (1) the vehicle group was given vehicle orally; (2) the FK506 group was given 0.15?mg/kg-1.d-1 FK506; and (3) the MMF group was given 20?mg/kg-1.d-1 MMF. At 4, 8, and 12?weeks post-transplantation, serum creatinine (SCr), collagen deposition, Connective tissue growth factor (CTGF), alpha smooth muscle actin (α-SMA) and E-cadherin expressions were determined and hematoxylin-eosin (HE) and Periodic acid-Schiff (PAS) stains were performed. Results Renal function progressively deteriorated and showed typical CAN morphology in the vehicle and FK506 groups, while SCr and inflammatory infiltration (Banff score) showed a significant decrease in the MMF group after 8?weeks post-transplantation compared with those in the other groups (p?α-SMA in the MMF group were significantly reduced, and the down-regulated expression of E-cadherin was abated (p? Conclusions MMF showed favorable effects on renal interstitial fibrosis, thus efficiently retarding the progression of CAN.