4.6 Article

Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-κB signaling pathway

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PLOS ONE
卷 12, 期 2, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0172006

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  1. National Natural Science Foundation of China (NSFC) [81471835, 81471889]
  2. Key Provincial Talents of Jiangsu Province [RC201107]
  3. Science and Technology Development Projects of Soochow [SYSD2013076]

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Aims To investigate whether dexmedetomidine (DEX) preconditioning could alleviate the inflammation caused by myocardial ischemia/reperfusion (I/R) injury by reducing HMGB1-TLR4MyD88-NF-kappa B signaling. Methods Seventy rats were randomly assigned into five groups: sham group, myocardial I/R group (I/R), DEX+I/R group (DEX), DEX+yohimbine+I/R group (DEX/YOH), and yohimbine+I/R group (YOH). Animals were subjected to 30 min of ischemia induced by occluding the left anterior descending artery followed by 120 min of reperfusion. Myocardial infarct size and histological scores were evaluated. The levels of IL-6 and TNF-alpha in serum and myocardium were quantified by enzyme-linked immunosorbent assay, and expression of HMGB1, TLR4, MyD88, I kappa B and NF-kappa B in the myocardial I/R area were determined with Western blot and immunocytochemistry. Results Myocardial infarct sizes, histological scores, levels of circulating and myocardial IL-6 and TNF-alpha, the expression of HMGB1, TLR4, MyD88 and NF-kappa B, and the degradation of I kappa B were significantly increased in the I/R group compared with the sham group (P<0.01). DEX preconditioning significantly reduced the myocardial infarct size and histological scores (P<0.01 vs. I/R group). Similarly, the serum and myocardial levels of IL-6 and TNF-alpha, the expression of HMGB1, TLR4, MyD88 and NF-kappa B, and the degradation of I kappa B were significantly reduced in the DEX group (P<0.01 vs. I/R group). These effects were partly reversed by yohimbine, a selective alpha(2)-adrenergic receptor antagonist, while yohimbine alone had no significant effect on any of the above indicators. Conclusion DEX preconditioning reduces myocardial I/R injury in part by attenuating inflammation, which may be attributed to the downregulation of the HMGB1-TLR4-MyD88-NF-kappa B signaling pathway mediated by the alpha 2-adrenergic receptor activation.

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