Diverse effects of ischemic pretreatments on the long-term renal damage induced by ischemia-reperfusion.

BACKGROUND/AIMS: The role of ischemic pretreatment in long-term changes after renal ischemia-reperfusion (I/R) injury remains unknown. In this study, we mainly aimed to investigate the effect of ischemic pretreatments with different durations on the development of tubulointerstitial fibrosis and functional impairment following acute renal I/R.

METHODS

We established a rat model of renal warm I/R, clamping both pedicles for 40 min followed by reperfusion; the experiment was followed up for 10 weeks. Prior ischemia (10, 20, 30 min) was induced 8 days before the 40-min ischemia. To assess tissue fibrosis, we performed morphometric analysis, Masson's trichrome and Sirius red staining. We also analyzed the expression of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta(1) (TGF-beta(1)) and phospho-Smad2.

RESULTS

Patchy tubulointerstitial fibrosis was found 5 and 10 weeks later in rats subjected to I/R alone or pretreated with 10-min ischemia. Tubulointerstitial fibrosis deteriorated further and renal dysfunction occurred in rats pretreated with 30-min ischemia accompanied by increased expression of alpha-SMA, TGF-beta(1), and phospho-Smad2 at 5 weeks. In contrast, the above abnormalities were significantly attenuated in rats pretreated with 20-min ischemia.

CONCLUSION

Severe I/R injury may cause tubulointerstitial fibrosis in the long term, and different ischemic pretreatments have diverse effects on renal fibrosis.