Influences of HIF-lα on Bax/Bcl-2 and VEGF expressions in rats with spinal cord injury

Int J Clin Exp Pathol. 2013 Oct 15;6(11):2312-22. eCollection 2013.

Abstract

Hypoxia-inducible factor 1-alpha (HIF-1α) is a subunit of HIF-l and thought to be able to protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. This study aimed to investigated whether recombinant adenovirus vector over-expressing HIF-lα could affect apoptosis-related proteins (Bcl-2 and Bax) and vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model. A total of 60 male SD rats were divided into 4 groups: Sham, Control, Ad-Blank and Ad-HIF-1α groups. 1, 3, 7, 14, 28 days after surgery, the behavioral recovery was evaluated with BBB scales. Then, rats were sacrificed and the spinal cord was collected for detection of Bcl-2, Bax and VEGF expressions by immunohistochemistry. Results showed the Bcl-2, Bax, VEGF and HIF-lα expressions increased in animals with SCI, but the increase in Bcl-2, VEGF and HIF-lα expressions were higher in Ad-HIF-1α group when compared with other groups, but Bax expression decreased significantly. In addition, administration of Ad-HIF-1α significantly reduced apoptotic cells and promoted the recovery of neurological function. In conclusion, administration of Ad-HIF-1α after SCI could ameliorate neuronal apoptosis and promote angiogenesis in rats. Our study provides a basis for further exploration of the relationship between HIF1α and SCI.

Keywords: HIF-1α; apoptosis; spinal cord injury; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Behavior, Animal
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • Neovascularization, Physiologic
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord / blood supply
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Time Factors
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism*
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Bax protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • vascular endothelial growth factor A, rat