Myocardial ischemia/reperfusion (I/R) injury is a serious threat to the health of people around the world. Recent evidence has indicated that high-mobility group box-1 (HMGB1) is involved in I/R-induced inflammation, and inflammation can cause necroptosis of cells. Interestingly, dexmedetomidine (DEX) has anti-inflammatory properties. Therefore, we speculated that DEX preconditioning may suppress H/R-induced necroptosis by inhibiting expression of HMGB1 in cardiomyocytes. We found that hypoxia/reoxygenation (H/R) significantly increased cellular damage, as measured by cell viability (100 ± 3.26% vs. 53.33 ± 3.29, p < 0.01), CK-MB (1 vs. 3.25 ± 0.26, p < 0.01), cTnI (1 vs. 2.69 ± 0.31, p < 0.01), inflammation as indicated by TNF-α (1 ± 0.09 vs. 2.57 ± 0.12, p < 0.01), IL-1β (1 ± 0.33 vs. 3.87 ± 0.41, p < 0.01) and IL-6 (1 ± 0.36 vs. 3.60 ± 0.45, p < 0.01), and necroptosis, which were accompanied by significantly increased protein levels of HMGB1. These changes [cellular damage as measured by cell viability (53.33 ± 3.29% vs. 67.59 ± 2.69%, p < 0.01), CK-MB (3.25 ± 0.26 vs. 2.27 ± 0.22, p < 0.01), cTnI (2.69 ± 0.31 vs. 1.90 ± 0.25, p < 0.01), inflammation as indicated by TNF-α (2.57 ± 0.12 vs. 1.75 ± 0.15, p < 0.01), IL-1β (3.87 ± 0.41 vs. 2.09 ± 0.36, p < 0.01) and IL-6 (3.60 ± 0.45 vs. 2.21 ± 0.39, p < 0.01), and necroptosis proteins] were inhibited by DEX preconditioning. We also found that silencing expression of HMGB1 reinforced the protective effects of DEX preconditioning and overexpression of HMGB1 counteracted the protective effects of DEX preconditioning. Thus, we concluded that DEX preconditioning inhibits H/R-induced necroptosis by inhibiting expression of HMGB1 in cardiomyocytes.
Ischemia/reperfusion Inflammation Necroptosis High-mobility group box-1 Dexmedetomidine
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We thank M. Arico from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
Jingyi Chen conceived and designed the project. Jingyi Chen performed the experiments with the help of Zhenzhen Jiang, Xing Zhou, Xingxing Sun, Jianwei Cao, Yongpan Liu, and Xianyu Wang. Jingyi Chen wrote the manuscript. All authors discussed the manuscript.
This study was supported by Taihe Hospital Science and Technology Project in 2018 to Dr. Chen, Jingyi (grant numbers: 2018JJXM046).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
This article does not contain any studies with human participants performed by any of the authors.
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