Sequential expression of TLR4 and its effects on the myocardium of rats with myocardial ischemia-reperfusion injury

Inflammation. 2008 Oct;31(5):304-12. doi: 10.1007/s10753-008-9079-x.

Abstract

This study was designed to explore the role of toll like receptor 4 (TLR4) in myocardial ischemia reperfusion injury (MI/RI). Male Sprague-Dawley rats were randomly divided into sham and IR groups (36/group). The rats were sacrificed at various times following reperfusion (0, 1/2, 1, 2, 4 and 8 h). The histopathological and ultrastructural changes in the myocardium were examined under a light microscope and a transmission electron microscope. The TLR4 protein and mRNA expression were detected by immunohistochemistry and real-time reverse transcription polymerase chain reaction, respectively. The levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the myocardium were measured by enzyme-linked immunosorbent assays. The injury to the myocardium was severe in the IR group, and there were no significant improvements in histopathology and ultrastructure of the myocardium during the first 8 h following reperfusion. Positive TLR4 protein staining was observed in both sham and IR groups. The TLR4 protein levels were significantly increased in the IR group, peaking at 1 h post reperfusion. Additionally, the TLR4 mRNA levels were also up-regulated in the IR group. At all time points, IR rats had significantly higher TNF-alpha and IL-6 levels than the sham rats (P<0.05). The TLR4 mRNA expression positively correlated with the levels of TNF-alpha and IL-6 (r=0.728 and 0.676, P<0.01). Myocardial TLR4 expression was elevated at the early stage of myocardial ischemia reperfusion. Activated TLR4 may play a role in MI/RI by increasing TNF-alpha and IL-6 expression.

MeSH terms

  • Animals
  • Electrocardiography / methods
  • Gene Expression Regulation*
  • Interleukin-6 / metabolism
  • Microscopy, Electron, Transmission
  • Models, Biological
  • Myocardial Reperfusion Injury / metabolism
  • Myocardium / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury*
  • Time Factors
  • Toll-Like Receptor 4 / biosynthesis*
  • Toll-Like Receptor 4 / physiology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • RNA, Messenger
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha