Possible Underlying Mechanisms of the Renoprotective Effect of Remote Limb Ischemic Preconditioning Against Renal Ischemia/Reperfusion Injury: A Role of Osteopontin, Transforming Growth Factor-Beta and Survivin

Abstract

Background: It has been documented that remote limb ischemic preconditioning (rIPC) protect kidneys against renal ischemia/reperfusion (I/R). We hypothesized that osteopontin (OPN), transforming growth factor beta (TGF-β), apoptotic proteins (survivin and caspase-3) and oxidative stress play role in the renoprotective effects of rIPC. Materials and Methods: Fifty-four male Sprague-Dawley rats were randomized into 3 equal groups: sham group, I/R group (left renal 45 min ischemia) and rIPC group (as I/R group with 3 cycles of left hind limb ischemia just before renal ischemia). Each group was subdivided into 24, 48 and 72 h groups according to the time of sacrifice. We measured serum creatinine and blood urea nitrogen (BUN) at the baseline and end points. Also, left kidney was harvested at study end points for assessment of the expression of OPN, TGF-β, apoptotic proteins (survivin and caspase-3) and oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) in kidney tissues and histopathological examination. Results: Serum creatinine and BUN levels and histopathological damage score were significantly lower in rIPC group than I/R group (p < 0.005). Also, compared to I/R group, the levels of MDA and the expression of OPN, TGF-β and caspase-3 in kidney tissues were significantly lower in rIPC group, while the levels of SOD and GSH and the expression of survivin in kidney tissues were significantly higher in rIPC group at all time points (p ≤ 0.05). Conclusions: rIPC exhibited protective effects against renal I/R injury which might be due to inhibition of OPN expression, inflammatory cytokine TGF-β and caspase-3 and activation of anti-apoptotic protein survivin as well as improvement of oxidative stress in kidney tissues.