Melatonin protects circulatory death heart from ischemia/reperfusion injury via the JAK2/STAT3 signalling pathway.

Author(s):

Lan H, Su Y, Liu Y, Deng C, Wang J, Chen T, Jules KED, Masau JF, Li H, Wei X

Keywords:

Categories:

Publication:

Life Sci. 2019 Jul 1;228:35-46.

Publication Link:

DOI Link:

https://doi.org/10.1016/j.lfs.2019.04.057

Aims

The shortage of donor hearts could be alleviated with the use of the allografts from donation after circulatory death (DCD). Here, we evaluated the protective effect of melatonin on myocardial ischemia/reperfusion (MI/R) injury in a DCD heart model after ex vivo perfusion.

Main Mthods

Donor hearts were harvested from DCD model rats pre-treated with or without melatonin and subjected to 30 min of ex vivo perfusion, followed by transplantation. Tissue samples were obtained at 3, 12, and 24 h after heart transplantation. Myocardial oedema was evaluated based on the water content and wet/dry ratio, while inflammation was examined with hematoxylin & eosin staining. The expression levels of matrix metalloproteinase-9, interleukin-6, and tumour necrosis factor-α were evaluated. Oxidative stress level was determined from the content of malondialdehyde, activities of superoxide dismutase and glutathione peroxidase, and expression of Nrf2, NQO1 and cytochrome-C. Myocardial apoptosis was detected with TUNEL assay and measurement of the expression levels of Bax, Bcl-2, caspase-3, and cleaved caspase-3. The activation of the JAK2/STAT3 signalling pathway was evaluated by determining the levels of p-JAK2 and p-STAT3.

Key Findings

Melatonin pre-treatment protected the heart from MI/R by reducing myocardial oedema and inflammation, attenuating oxidative stress, and decreasing myocardial apoptosis. Furthermore, the JAK2/STAT3 signalling pathway was activated after melatonin treatment during MI/R. The protective effects of melatonin were abolished by AG490.

Significance

Melatonin pre-treatment protected the heart from MI/R in a DCD heart model after ex vivo perfusion. Melatonin exerted cardioprotective effects through the activation of the JAK2/STAT3 signalling pathway.

Copyright © 2019 Elsevier Inc. All rights reserved.

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