Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway
Background Sevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2–STAT3) plays an important role in cardioprot...
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PeerJ Inc.
2017-04-01
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| Online Access: | https://peerj.com/articles/3196.pdf |
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| author | Jianjiang Wu Jin Yu Peng Xie Yiliyaer Maimaitili Jiang Wang Long Yang Haiping Ma Xing Zhang Yining Yang Hong Zheng |
| author_facet | Jianjiang Wu Jin Yu Peng Xie Yiliyaer Maimaitili Jiang Wang Long Yang Haiping Ma Xing Zhang Yining Yang Hong Zheng |
| author_sort | Jianjiang Wu |
| collection | DOAJ |
| description | Background Sevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2–STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2–STAT3 signal pathway. Methods An adult male Sprague–Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus. At the beginning of reperfusion, 2.4% sevoflurane alone or in combination with AG490 (a JAK2 selective inhibitor) was used as a postconditioning treatment. The cardiac function indicators, myocardial infarct size, lactic dehydrogenase (LDH) release, mitochondrial ultrastructure, mitochondrial reactive oxygen species (ROS) generation rates, ATP content, protein expression of p-JAK, p-STAT3, Bcl-2 and Bax were measured. Results Compared with the I/R group, S-post significantly increased the expression of p-JAK, p-STAT3 and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the myocardial infarction areas, improved the cardiac function indicators and the mitochondrial ultrastructure, decreased the mitochondrial ROS and increased the ATP content. However, the cardioprotective effects of S-post were abolished by treatment with a JAK2 selective inhibitor (p < 0.05). Conclusion This study demonstrates that the cardioprotective effects of S-post are associated with the activation of JAK2–STAT3. The mechanism may be related to an increased expression of p-JAK2 and p-STAT3 after S-post, which reduced mitochondrial ROS generation and increased mitochondrial ATP content, thereby reducing apoptosis and myocardial infarct size. |
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| last_indexed | 2024-03-09T06:32:12Z |
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| spelling | doaj.art-a0da8fb5d358442e94ab56b0f8b131e92023-12-03T11:03:59ZengPeerJ Inc.PeerJ2167-83592017-04-015e319610.7717/peerj.3196Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathwayJianjiang Wu0Jin Yu1Peng Xie2Yiliyaer Maimaitili3Jiang Wang4Long Yang5Haiping Ma6Xing Zhang7Yining Yang8Hong Zheng9Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Aerospace Medicine, Fourth Military Medical University, Xi’an, Shanxi, ChinaDepartment of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaBackground Sevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2–STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2–STAT3 signal pathway. Methods An adult male Sprague–Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus. At the beginning of reperfusion, 2.4% sevoflurane alone or in combination with AG490 (a JAK2 selective inhibitor) was used as a postconditioning treatment. The cardiac function indicators, myocardial infarct size, lactic dehydrogenase (LDH) release, mitochondrial ultrastructure, mitochondrial reactive oxygen species (ROS) generation rates, ATP content, protein expression of p-JAK, p-STAT3, Bcl-2 and Bax were measured. Results Compared with the I/R group, S-post significantly increased the expression of p-JAK, p-STAT3 and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the myocardial infarction areas, improved the cardiac function indicators and the mitochondrial ultrastructure, decreased the mitochondrial ROS and increased the ATP content. However, the cardioprotective effects of S-post were abolished by treatment with a JAK2 selective inhibitor (p < 0.05). Conclusion This study demonstrates that the cardioprotective effects of S-post are associated with the activation of JAK2–STAT3. The mechanism may be related to an increased expression of p-JAK2 and p-STAT3 after S-post, which reduced mitochondrial ROS generation and increased mitochondrial ATP content, thereby reducing apoptosis and myocardial infarct size.https://peerj.com/articles/3196.pdfApoptosisJAK2–STAT3 pathwayReactive oxygen speciesSevoflurane postconditioningIschemia–reperfusion injury |
| spellingShingle | Jianjiang Wu Jin Yu Peng Xie Yiliyaer Maimaitili Jiang Wang Long Yang Haiping Ma Xing Zhang Yining Yang Hong Zheng Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway PeerJ Apoptosis JAK2–STAT3 pathway Reactive oxygen species Sevoflurane postconditioning Ischemia–reperfusion injury |
| title | Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway |
| title_full | Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway |
| title_fullStr | Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway |
| title_full_unstemmed | Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway |
| title_short | Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway |
| title_sort | sevoflurane postconditioning protects the myocardium against ischemia reperfusion injury via activation of the jak2 stat3 pathway |
| topic | Apoptosis JAK2–STAT3 pathway Reactive oxygen species Sevoflurane postconditioning Ischemia–reperfusion injury |
| url | https://peerj.com/articles/3196.pdf |
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