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

被引:74
作者
Zhang, Jing-jing [1 ]
Peng, Ke [1 ]
Zhang, Juan [1 ]
Meng, Xiao-wen [1 ]
Ji, Fu-hai [1 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Anesthesiol, Suzhou, Peoples R China
来源
PLOS ONE | 2017年 / 12卷 / 02期
基金
中国国家自然科学基金;
关键词
ISCHEMIA-REPERFUSION INJURY; MOBILITY GROUP BOX-1; NF-KAPPA-B; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; ENDOTOXIN-INDUCED SHOCK; INFLAMMATORY RESPONSES; SARCOPLASMIC-RETICULUM; MICE; ACTIVATION; PROTEIN;
D O I
10.1371/journal.pone.0172006
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:15
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