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Anti-inflammatory effect of exendin-4 postconditioning during myocardial ischemia and reperfusion

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Abstract

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I/R) injury. Preconditioning of exendin-4 (Ex), a glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial I/R injury. The current study investigated whether Ex postconditioning also attenuated myocardial I/R injury and the potential mechanisms. Anesthetized male rats were subjected to ischemia for 30 min and treated with Ex (5 μg/kg, i.v.) 5 min before reperfusion, in the absence and/or presence of exendin (9–39) (an antagonist of glucagon-like peptide-1 receptor, 5 μg/kg, i.v.), followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-α, interleukin-6, and infarct size were measured. HMGB1 expression was assessed by immunoblotting. Postconditioning with Ex significantly decreased infarct size and levels of LDH and CK after 4 h reperfusion (all p < 0.05). Ex also significantly inhibited the increase in malondialdehyde level and decreased the level of superoxide dismutase (both p < 0.05). In addition, the increase in HMGB1 expression induced by I/R was significantly attenuated by Ex postconditioning. Administration of exendin (9–39) abolished the protective effect of Ex postconditioning (all p < 0.05). The present study suggests that Ex postconditioning may attenuate myocardial I/R injury, which may in turn be associated with inhibiting inflammation.

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Acknowledgments

This study was partially supported by a grant from the National Natural Science foundation of China (No. 81100146 and 81370308), Grant 111023 from the Fundamental Research Funds for the Central Universities, the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20110141120060), and the Fundamental Research Funds of Wuhan City (No. 2013070104010044).

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Authors and Affiliations

  1. Department of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, China

    Xianjin Du & Jie Wei

  2. Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, China

    Xiaorong Hu

  3. Department of Cardiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China

    Xiaorong Hu

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  1. Xianjin Du
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  2. Xiaorong Hu
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  3. Jie Wei
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Correspondence to Xiaorong Hu or Jie Wei.

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Du, X., Hu, X. & Wei, J. Anti-inflammatory effect of exendin-4 postconditioning during myocardial ischemia and reperfusion. Mol Biol Rep 41, 3853–3857 (2014). https://doi.org/10.1007/s11033-014-3252-0

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  • DOI: https://doi.org/10.1007/s11033-014-3252-0

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