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Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion

  • Authors:
    • Shan Liu
    • Yang Yang
    • Yan Qiu Song
    • Jie Geng
    • Qing Liang Chen
  • View Affiliations / Copyright

    Affiliations: Tianjin Cardiovascular Institute, Tianjin Chest Hospital, Tianjin 300222, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5102-5108
    |
    Published online on: February 2, 2018
       https://doi.org/10.3892/mmr.2018.8543
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Abstract

To explore the protective effect of N(2)-L-alanyl-L-glutamine (NLAG) on myocardial ischemia-reperfusion injury (IRI), and observe the influence of NLAG on the Janus activated kinase signal transducer 2 and activator of transcription 3 (JAK2/STAT3) signaling pathway‑associated molecules. Wistar rats were randomly divided into three groups: Sham, IRI and NLAG. In the IRI rat model, the cardiac hemodynamics, the maximum rate of left ventricular pressure (+dP/dtmax) and the left ventricular end‑diastolic pressure (LVDP) were recorded. Hematoxylin‑eosin and Masson staining were used to detect myocardial histological changes. The levels of plasma interleukin (IL)‑1β and ‑6, tumor necrosis factor (TNF)‑α, lactase dehydrogenase (LDH), troponin (cTn)I, creatine kinase (CK), heart type fatty acid binding protein (hFABP), malondialdehyde (MDA) and succinate dehydrogenase (SDH) were determined with ELISA. The protein expression levels of B‑cell lymphoma (Bcl)‑2, Bcl2‑associated X protein (Bax), Caspase‑3, JAK2, phosphorylated (p)‑JAK2, STAT3 and p‑STAT3 were detected by western blot analysis. The IRI model demonstrated notable myocardial injury; myocardial cells were arranged disorderly with some nuclei disappearing, and cardiac muscular fibers were degenerated. Following 60 min of reperfusion, LVDP, HR and +dP/dtmax were 31.3±4.53 mmHg, 239.17±8.45 beats/min and 615.17 mmHg/sec, respectively. Compared with the Sham group, the levels of LDH, cTnI, CK, hFABP release, inflammatory factors (IL‑1β, IL‑6 and TNF‑α) and oxygen free radical (MDA and SDH) levels were increased in the IRI group. In the NLAG group, myocardial injury was improved, the concentrations of LDH, cTnI, CK, hFABP, IL‑1β, IL‑6, TNF‑α, MDA were decreased, and SDH release was increased compared with the IRI group. In addition, NLAG significantly increased Bcl‑2, JAK2, p‑JAK2, STAT3 and p‑STAT3 protein expression, and decreased Bax protein expression compared with the IRI group. In conclusion, myocardial ischemia‑reperfusion can lead to myocardial cell apoptosis and myocardial injury and NLAG attenuates the IRI‑induced mitochondrial oxidative stress injury and apoptosis by activating the JAK2/STAT3 signaling pathway, thus exerting protective effects against IRI.
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Copy and paste a formatted citation
Spandidos Publications style
Liu S, Yang Y, Song Y, Geng J and Chen Q: Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion. Mol Med Rep 17: 5102-5108, 2018.
APA
Liu, S., Yang, Y., Song, Y., Geng, J., & Chen, Q. (2018). Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion. Molecular Medicine Reports, 17, 5102-5108. https://doi.org/10.3892/mmr.2018.8543
MLA
Liu, S., Yang, Y., Song, Y., Geng, J., Chen, Q."Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion". Molecular Medicine Reports 17.4 (2018): 5102-5108.
Chicago
Liu, S., Yang, Y., Song, Y., Geng, J., Chen, Q."Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion". Molecular Medicine Reports 17, no. 4 (2018): 5102-5108. https://doi.org/10.3892/mmr.2018.8543
Copy and paste a formatted citation
x
Spandidos Publications style
Liu S, Yang Y, Song Y, Geng J and Chen Q: Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion. Mol Med Rep 17: 5102-5108, 2018.
APA
Liu, S., Yang, Y., Song, Y., Geng, J., & Chen, Q. (2018). Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion. Molecular Medicine Reports, 17, 5102-5108. https://doi.org/10.3892/mmr.2018.8543
MLA
Liu, S., Yang, Y., Song, Y., Geng, J., Chen, Q."Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion". Molecular Medicine Reports 17.4 (2018): 5102-5108.
Chicago
Liu, S., Yang, Y., Song, Y., Geng, J., Chen, Q."Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion". Molecular Medicine Reports 17, no. 4 (2018): 5102-5108. https://doi.org/10.3892/mmr.2018.8543
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