Sequential expression of TLR4 and its effects on the myocardium of rats with myocardial ischemia-reperfusion injury.
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.
Yang
Jun
J
Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
Yang
Jian
J
Ding
Jia-wang
JW
Chen
Li-hua
LH
Wang
Yan-lin
YL
Li
Song
S
Wu
Hui
H
D000818:Animals; D004562:Electrocardiography / Q000379:methods; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha