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Sequential Expression of TLR4 and its Effects on the Myocardium of Rats with Myocardial Ischemia-Reperfusion Injury

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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 ultrastructual 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)-α 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-α and IL-6 levels than the sham rats (P < 0.05). The TLR4 mRNA expression positively correlated with the levels of TNF-α 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-α and IL-6 expression.

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Acknowledgements

We thank Professors C. Zhang and L. Han of the Faculty of the Microbiology Department, Professor Y. Hu and Dr. B. Gao of the Department of Pathology of the First College of Clinical Medical Sciences, and the China Three Gorges University for their helpful discussions and suggestions on this work.

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Authors and Affiliations

  1. Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei Province, China

    Jun Yang, Jian Yang, Li-hua Chen, Song Li & Hui Wu

  2. Department of Cardiology, Yichang Central People’s Hospital, Yichang, 443000, Hubei Province, China

    Jia-wang Ding

  3. The Institute of Molecular Biology, China Three Gorges University, Yichang, 443000, Hubei Province, China

    Yan-lin Wang

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  1. Jun Yang
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Correspondence to Jian Yang.

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Yang, J., Yang, J., Ding, Jw. et al. Sequential Expression of TLR4 and its Effects on the Myocardium of Rats with Myocardial Ischemia-Reperfusion Injury. Inflammation 31, 304–312 (2008). https://doi.org/10.1007/s10753-008-9079-x

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