Role of high‑mobility group box‑1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate

Lin,Yunling; Chen,Lianglong; Li,Weiwei; Fang,Jun

doi:10.3892/etm.2015.2290

Role of high‑mobility group box‑1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate

Authors:
- Yunling Lin
- Lianglong Chen
- Weiwei Li
- Jun Fang
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Affiliations: Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, P.R. China
Published online on: February 13, 2015 https://doi.org/10.3892/etm.2015.2290
Pages: 1537-1541

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Abstract

High‑mobility group box‑1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential role of HMGB1 in a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In protocol 1, the rats were assigned to one of four groups (n=16 per group): Phosphate‑buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three different doses (1, 10 or 100 µg/kg). In protocol 2, the rats were also assigned to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP (40 mg/kg) or rhHMGB1 (100 µg/kg) was injected intravenously prior to reperfusion. Hemodynamic measurements were performed, and myocardial infarct size (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6) expression levels. In the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 µg/kg) group compared with that in the PBS group, and this increase was accompanied by elevated levels of TNF‑α and IL‑6. In the protocol 2 rats, I/R resulted a 4.8‑fold increase in HMGB1 expression with an increased IS and impaired cardiac function compared with the sham group. EP significantly inhibited the elevated HMGB1 level, suppressed the activated TNF‑α and IL‑6 and reduced cardiac dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion, accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP can exert a strong protective effect against myocardial I/R injury, and these benefits are associated with a reduction in HMGB1.

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