title: Diverse effects of ischemic pretreatments on the long-term renal damage induced by ischemia-reperfusion.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Severe I/R injury may cause tubulointerstitial fibrosis in the long term, and different ischemic pretreatments have diverse effects on renal fibrosis.
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianzhou
authors.initials: J
authors.lastname: Zou
authors.forename: Xunhui
authors.initials: X
authors.lastname: Xu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Ding
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D005355:Fibrosis; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control*; D051899:Smad2 Protein / Q000378:metabolism; D013696:Temperature; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D053773:Transforming Growth Factor beta1