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Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway

  • Authors:
    • Bo Liao
    • Zhongyuan Han
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Cardiovascular Medicine, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, P.R. China
    Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 302
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    Published online on: May 9, 2023
       https://doi.org/10.3892/etm.2023.12001
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Abstract

Myocardial tissue cell damage induced by myocardial ischemia/reperfusion (MI/R) notably elevates the mortality rate, increases the complications of patients with myocardial infarction and decreases reperfusion benefit in patients suffering from acute myocardial infarction. Roflumilast protect against cardiotoxicity. Therefore, the present study aimed to investigate the effect of roflumilast on MI/R injury and the underlying mechanisms. To simulate MI/R in vivo and in vitro, the rat model of MI/R was established and H9C2 cells were subjected to hypoxia/reoxygenation (H/R) induction, respectively. The myocardial infarction areas were observed by 2,3,5‑triphenyltetrazolium chloride staining. The myocardial enzyme levels in serum and levels of inflammatory cytokines and oxidative stress markers in cardiac tissue were assessed by corresponding assay kits. The cardiac damage was observed by hematoxylin and eosin staining. The mitochondrial membrane potential in cardiac tissue and H9C2 cells was detected using the JC‑1 staining kit. The viability and apoptosis of H9C2 cells were detected by Cell Counting Kit‑8 and TUNEL assay, respectively. The levels of inflammatory cytokines, oxidative stress markers and ATP in H/R‑induced H9C2 cells were analyzed by corresponding assay kits. Western blotting was used for the estimation of AMP‑activated protein kinase (AMPK) signaling pathway‑, apoptosis‑ and mitochondrial regulation‑associated protein levels. The mPTP opening was detected using a calcein‑loading/cobalt chloride‑quenching system. The results indicated that roflumilast decreased MI/R‑induced myocardial infarction by alleviating myocardial injury and mitochondrial damage through the activation of the AMPK signaling pathway. In addition, roflumilast mitigated viability damage, alleviated oxidative stress, attenuated the inflammatory response and decreased mitochondrial damage in H/R‑induced H9C2 cells by activating the AMPK signaling pathway. However, compound C, an inhibitor of the AMPK signaling pathway, reversed the effect of roflumilast on H/R‑induced H9C2 cells. In conclusion, roflumilast alleviated myocardial infarction in MI/R rats and attenuated H/R‑induced oxidative stress, inflammatory response and mitochondrial damage in H9C2 cells by activating the AMPK signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Liao B and Han Z: Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway. Exp Ther Med 25: 302, 2023.
APA
Liao, B., & Han, Z. (2023). Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway. Experimental and Therapeutic Medicine, 25, 302. https://doi.org/10.3892/etm.2023.12001
MLA
Liao, B., Han, Z."Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway". Experimental and Therapeutic Medicine 25.6 (2023): 302.
Chicago
Liao, B., Han, Z."Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway". Experimental and Therapeutic Medicine 25, no. 6 (2023): 302. https://doi.org/10.3892/etm.2023.12001
Copy and paste a formatted citation
x
Spandidos Publications style
Liao B and Han Z: Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway. Exp Ther Med 25: 302, 2023.
APA
Liao, B., & Han, Z. (2023). Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway. Experimental and Therapeutic Medicine, 25, 302. https://doi.org/10.3892/etm.2023.12001
MLA
Liao, B., Han, Z."Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway". Experimental and Therapeutic Medicine 25.6 (2023): 302.
Chicago
Liao, B., Han, Z."Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway". Experimental and Therapeutic Medicine 25, no. 6 (2023): 302. https://doi.org/10.3892/etm.2023.12001
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