Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

PeerJ

article

Jianjiang Wu¹  Jin Yu¹  Peng Xie¹  Yiliyaer Maimaitili¹  Jiang Wang¹  Long Yang¹  Haiping Ma¹  Xing Zhang²  Yining Yang³  Hong Zheng¹ 

[1] Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University;Department of Aerospace Medicine, Fourth Military Medical University;Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University

关键词: Apoptosis;    JAK2–STAT3 pathway;    Reactive oxygen species;    Sevoflurane postconditioning;    Ischemia–reperfusion injury;   

DOI  :  10.7717/peerj.3196

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

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