Ischemic Postconditioning Inhibits the Renal Fibrosis Induced by Ischemia-reperfusion Injury in Rats

OBJECTIVE To investigate whether ischemic postconditioning effects on the development of tubulointerstitial fibrosis follow acute renal ischemia-reperfusion. METHODS Rat models of warm renal I/R were established by clamping left pedicles for 45 minutes after right nephrectomy, both with and without treatment with ischemic postconditioning, and then reperfused for up to 12 weeks. Hematoxylin-eosin (H&E) and Masson's trichrome staining were used to assess renal fibrosis. The expression spot and protein levels of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta 1 (TGF-beta 1), and phospho-Smad2 were also analyzed. RESULTS Our data showed that patchy inflammation and tubulointerstitial fibrosis were found 12 weeks later in rats subjected to I/R alone or with postconditioning. Tubulointerstitial fibrosis worsened further in rats subjected to 45-minute ischemia-reperfusion, accompanied by the increased expressions of alpha-SMA, TGF-beta 1, and phospho-Smad2 at the end of 12 weeks. In contrast, the above histologic changes and molecular expressions were significantly attenuated in rats of ischemic postconditioning group. CONCLUSION The results indicated that 45-minute I/R injury may cause tubulointerstitial fibrosis in the long term, and ischemic postconditioning has beneficial effects on renal fibrosis. Its mechanisms may involve inhibition of the TGF-beta 1/phospho-Smad2 pathway to exert protective effects. UROLOGY 80: 484.e1-484.e7, 2012. (c) 2012 Elsevier Inc.