The SNHG10-miR-495-3p-PTEN axis is involved in sevoflurane-mediated protective effects in cardiomyocytes against hypoxia/reoxygenation injury

  • Toxicol In Vitro. 2023 Oct 24:105724. doi: 10.1016/j.tiv.2023.105724.
Jiandong He  1 ,  Jing Yu  1 ,  Chongfang Han  2 ,  Wenqu Yang  1 ,  Chunmin Zhang  1 ,  Weihong Hao  1 ,  Yinlei Duan  1
Affiliations
  • 1. Department of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, Shanxi, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
  • 2. Department of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, Shanxi, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: [email protected].
PMID: 37884162 DOI: 10.1016/j.tiv.2023.105724
Abstract

Myocardial infarction (MI) has been considered a leading cause of death worldwide. Relieving ischemia-reperfusion myocardial damage is one of the major roles in treating MI. Sevoflurane postconditioning provides myocardial protection, and this study probes the mechanism of sevoflurane-mediated protective effects. A hypoxia/reoxygenation (H/R) model was constructed in cardiomyocytes, which were pretreated with 2.4% sevoflurane. Alterations in SNHG10, miR-495-3p, and PTEN levels were determined, and gain- or loss-of functional assays were conducted to confirm the role of the SNHG10/miR-495-3p axis, which is potentially regulated by sevoflurane. Cell viability, oxidative stress, and inflammatory reactions were all evaluated. The results indicated that sevoflurane post-conditioning attenuated H/R-induced cardiomyocyte damage and reduced the SHNH10 level. SNHG10 overexpression reversed sevoflurane-mediated protective effects on cardiomyocytes. Moreover, SNHG10 targeted miR-495-3p and restrained its expression, while miR-495-3p targeted PTEN, suppressed PTEN levels, and promoted HIF-1α expression. miR-495-3p overexpression decreased SNHG10-mediated myocardial injury and enhanced HIF-1α levels. However, no additional protection was found when sevoflurane was administered to H/R-exposed cardiomyocytes following treatment with the HIF-1α Inhibitor LW6. Overall, sevoflurane protects cardiomyocytes from H/R by modulating the SNHG10-miR-495-3p-PTEN-HIF-1α axis.

Keywords
Cardiomyocyte; Hypoxia; PTEN; SNHG10; Sevoflurane; miR-495-3p.
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