Ischemic preconditioning increases endothelial progenitor cell number to attenuate partial nephrectomy-induced ischemia/reperfusion injury

PLoS One. 2013;8(1):e55389. doi: 10.1371/journal.pone.0055389. Epub 2013 Jan 31.

Abstract

Objectives: The objective of this study was to investigate the role of endothelial progenitor cells (EPCs) in the modulation of ischemia-reperfusion injury (IRI) in a partial nephrectomy (PN) rat model using early-phase ischemic preconditioning (IPC).

Materials and methods: Ninety male Sprague-Dawley rats were randomly divided into three groups following right-side nephrectomy: Sham-operated rats (surgery without vascular clamping); PN rats (renal blood vessels were clamped for 40 min and PN was performed); and IPC rats (pretreated with 15 min ischemia and 10 min reperfusion). At 1, 3, 6, 12, 24 h, and 3 days after reperfusion, the pool of circulating EPCs and kidneys were harvested. The extent of renal injury was assessed, along with EPC number, cell proliferation, angiogenesis, and vascular growth factor expression.

Results: Pretreated rats exhibited significant improvements in renal function and morphology. EPC numbers in the kidneys were increased at 12 h following reperfusion in the IPC group as compared to the PN or Sham groups. Cell proliferation (including endothelial and tubular epithelial cells) and angiogenesis in peritubular capillaries were markedly increased in kidneys treated with IPC. In addition, vascular endothelial growth factor-A (VEGF-A) and stromal cell-derived factor-1α (SDF-1α) expression in the kidneys of pretreated rats was increased compared to rats subjected to PN.

Conclusions: OUR INVESTIGATION SUGGESTED THAT: (1) the early phase of IPC may attenuate renal IRI induced by PN; (2) EPCs play an important role in renal protection, involving promotion of cell proliferation and angiogenesis through release of several angiogenic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Chemokine CXCL12 / metabolism
  • DNA Primers / genetics
  • Endothelial Cells / physiology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Histological Techniques
  • Immunohistochemistry
  • Ischemic Preconditioning / methods*
  • Male
  • Neovascularization, Physiologic / physiology
  • Nephrectomy / adverse effects*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / prevention & control*
  • Stem Cells / physiology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Chemokine CXCL12
  • DNA Primers
  • Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81070597), the Open Key Program of the Jiangsu Province Health Bureau (KF200942), Science and Education Development Program of the Jiangsu Province Health Board (LJ201107) and Six Talent Peaks of the Jiangsu Province Health Bureau(2011-WS-093). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.