Dexmedetomidine ameliorates ischemia-induced nerve injury by up-regulating Sox11 expression

Qiong Wang; Na Zhang; Xue Bai; Jianhua Liu; Xiaobao Bi; Yonghong Tan

doi:10.21037/atm-22-6639

Dexmedetomidine ameliorates ischemia-induced nerve injury by up-regulating Sox11 expression

Ann Transl Med. 2023 Feb 15;11(3):153. doi: 10.21037/atm-22-6639. Epub 2023 Feb 10.

Authors

Qiong Wang^#¹, Na Zhang^#¹, Xue Bai¹, Jianhua Liu¹, Xiaobao Bi¹, Yonghong Tan¹

Affiliation

¹ Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Dexmedetomidine (Dex) is associated with several biological processes. Ischemic stroke has the characteristics of high morbidity and mortality. Herein, we aimed to explore whether Dex ameliorates ischemia-induced injury and determine its mechanism.

Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were used to measure gene and protein expression. Cellular viability and proliferation were assessed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays, respectively. Cell apoptosis was detected by flow cytometry. An oxygen-glucose deprivation/reoxygenation model of SK-N-SH and SH-SY5Y cells was constructed. A middle cerebral artery occlusion (MCAO) model was also built to assess Dex function in vivo. Neuronal function was assessed using the Bederson Behavior Score and Longa Behavior Score.

Results: We found that Dex positively and dose-dependently regulated Sox11 expression and prevented damage caused by oxygen-glucose deprivation/reoxygenation (OGD/R), enhancing cell viability and proliferation and reducing apoptosis in SK-N-SH and SH-SY5Y cells. The overexpression of Sox11 antagonized OGD/R-induced SK-N-SH and SH-SY5Y cell apoptosis and promoted cell growth in vitro. Furthermore, cell proliferation was decreased and cell apoptosis was increased after Sox11 knockdown in Dex-treated SK-N-SH and SH-SY5Y cells. We demonstrated that Dex prevented OGD/R-induced cell injury by up-regulating Sox11. Furthermore, we also confirmed that Dex protected rat from ischemia-induced injury in the MCAO model.

Conclusions: The role of Dex in cell viability and survival was verified in this study. Moreover, Dex protected neurons from MCAO-induced injury by up-regulating the expression of Sox11. Our research proposes a potential drug to improve the functional recovery of stroke patients in the clinic.

Keywords: Ischemic stroke; Sox11; dexmedetomidine (Dex); middle cerebral artery occlusion (MCAO); oxygen-glucose deprivation/reoxygenation (OGD/R).