Expression imbalance of transcription factors GATA-3 and T-bet in post-resuscitation myocardial immune dysfunction in a porcine model of cardiac arrest

Resuscitation. 2013 Jun;84(6):848-53. doi: 10.1016/j.resuscitation.2012.11.023. Epub 2012 Nov 29.

Abstract

Background: This study investigated whether an imbalance in Th1/Th2 cells is involved in the post-resuscitation myocardial immune dysfunction.

Methods: 26 Wuzhishan miniature pigs were randomly divided into return of spontaneous circulation (ROSC) group (n=20) and sham-operated group (n=6), 20 pigs were subjected to 8min of electrically induced cardiac arrest, After successful ROSC, the 16 surviving pigs were randomly assigned to be sacrificed (n=8 per group) at 12 and 24h after ROSC, respectively. CD4(+) and CD8(+) lymphocyte subsets were determined by flow cytometry, interleukin (IL)-4 and interferon (IFN)-γ in the myocardium were measured by ELISA, and protein and mRNA levels of GATA-3 and T-bet were detected in the myocardium by Western blotting and quantitative real-time PCR in the post-ROSC group (n=8 per group) at 12 and 24h after ROSC and sham-operated group (n=6) at 24h after ROSC, respectively.

Results: CD4(+) lymphocyte subsets were significantly lower in the post-ROSC group compared with the sham-operated group (P<0.05) at 12 and 24h after ROSC. The levels of myocardium IFN-γ were markedly increased, while IL-4 was significantly decreased in the post-ROSC group compared with the sham-operated group (P<0.05) at 12 and 24h after ROSC. Protein expression and mRNA levels of T-bet were markedly increased in the myocardium of pigs in the post-ROSC group compared with the sham-operated group (P<0.05) at 12 and 24h after ROSC, while GATA-3 was significantly reduced (P<0.05).

Conclusion: The myocardial immune dysfunction induced by the change in expression levels of the transcription factors GATA-3 and T-bet may be involved in the process of post-resuscitation myocardial injury in a porcine model of cardiac arrest.

MeSH terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cardiopulmonary Resuscitation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • GATA3 Transcription Factor / genetics*
  • Gene Expression Regulation / physiology*
  • Heart Arrest / genetics*
  • Heart Arrest / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Male
  • Myocardium / immunology*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Swine
  • Swine, Miniature
  • T-Box Domain Proteins / genetics*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • GATA3 Transcription Factor
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-4
  • Interferon-gamma