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However, the molecular mechanisms involved remain to be clarified. In this study, we intend to investigate the effects of BMSC\u2010derived conditioned medium (BMSC\u2010CM) on hypoxia\/reoxygenation (H\/R)\u2010induced injury of H9c2 myocardial cells, and the potential mechanisms. Cell injury was determined through level of cell viability, lactate dehydrogenase (LDH) release, total intracellular reactive oxygen species (ROS), mitochondrial membrane potential (\u0394\u03c8m), and cell apoptosis. Autophagic activity of cells was detected through levels of the autophagy\u2010associated proteins and autophagic flux. Results showed that BMSC\u2010CM alleviated H\/R\u2010induced injury in H9c2 cells, as demonstrated by increased cell viability and \u0394\u03c8m, decreased ROS production, LDH release, and cell apoptosis. Furthermore, the H\/R treatment induced a decrease in autophagic activity and an increase in Notch2 signaling activation in H9c2 cells. In the presence of BMSC\u2010CM, the autophagic activity impaired by the H\/R treatment was upregulated with decreased phosphorylation of mTOR, and the activation of Notch2 signaling was downregulated. These effects of BMSC\u2010CM could be replicated by Notch signaling inhibitor. In contrast, inhibitors of cell autophagy including chloroquine (CQ) and 3\u2010methyladenine, diminished the protective effects of BMSC\u2010CM. Taken together results, our study showed that BMSC\u2010CM could protect H9c2 cells from H\/R\u2010induced injury potentially through regulating Notch2\/mTOR\/autophagy signaling. These findings may provide a novel insight into the mechanisms of BMSC\u2010CM in therapy of myocardial ischemia\/reperfusion injury as well as other ischemic diseases.<\/jats:p>","DOI":"10.1002\/jcp.28530","type":"journal-article","created":{"date-parts":[[2019,4,6]],"date-time":"2019-04-06T07:12:49Z","timestamp":1554534769000},"page":"18906-18916","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Bone marrow mesenchymal stem cells\u2010derived conditioned medium protects cardiomyocytes from hypoxia\/reoxygenation\u2010induced injury through Notch2\/mTOR\/autophagy signaling"],"prefix":"10.1002","volume":"234","author":[{"given":"Xianyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathophysiology\u00a0&amp; Hubei Province Key Laboratory of Allergy and Immunology School of Basic Medical Sciences, Wuhan University Wuhan China"},{"name":"Department of Pathophysiology School of Basic Medical Sciences, Hubei University of Medicine Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology\u00a0&amp; 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