Protective effect and mechanism of dexmedetomidine on hypoxia-reoxygenated myocardial cells

WANG Yanping; XU Yizhen; YUAN Yingchuan; Guli. YAKEFU; CHEN Zhengwen; CHEN Aifang

doi:10.7619/jcmp.20230238

Journal of Clinical Medicine in Practice > 2023 > 27(11): 108-113, 119. > DOI: 10.7619/jcmp.20230238

WANG Yanping, XU Yizhen, YUAN Yingchuan, Guli. YAKEFU, CHEN Zhengwen, CHEN Aifang. Protective effect and mechanism of dexmedetomidine on hypoxia-reoxygenated myocardial cells[J]. Journal of Clinical Medicine in Practice, 2023, 27(11): 108-113, 119. DOI: 10.7619/jcmp.20230238

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Protective effect and mechanism of dexmedetomidine on hypoxia-reoxygenated myocardial cells

Department of Anesthesiology, the Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830063

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Received Date: February 02, 2023
Revised Date: April 09, 2023
Available Online: June 24, 2023

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Abstract

Abstract

Objective
To investigate the protective effect and mechanism of dexmedetomidine (Dex) on hypoxia-reoxygenated (H/R) cardiomyocytes.
Methods
H9C2 cells were selected to construct a H/R cell injury model (H/R group), and normal cultured cells were used as the control group. The cells treated with Dex for 24 h before H/R treatment were defined as H/R+Dex group. Vector and microRNA (miR)-138-5p mimic plasmids transfected into H9C2 cells after H/R treatment were defined as H/R+Vector group and H/R+miR-138-5p group. Vector and miR-138-5p mimic plasmids were co-transfected with MUT-SOX9 and WT-SOX9 vectors, and then transfected into H9C2 cells, which were defined as mutant type (MUT)-SOX9+Vector group, MUT- sex-determining region Y box protein 9 (SOX9)+miR-138-5p group, WT-SOX9+Vector group and wild type (WT)-SOX9+miR-138-5p group. Cell Counting Kit-8 (CCK-8) was conducted to perform cell proliferation; flow cytometry was conducted to perform apoptosis; enzyme-linked reaction adsorption assay (ELISA) was conducted to perform cell supernatant superoxide dismutase (SOD), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels; the real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was conducted to perform miR-138-5p expression; Weston blot was conducted to perform TNF-α, IL-6, leukocyte lymphoma-2 (Bcl-2), and Bcl-related X protein (Bax) and SOX9 expression; the luciferase reporter assay was performed to detect the targeting relationship between miR-138-5p and SOX9.
Results
Compared with the control group, cell proliferation viability, apoptosis rate, expression of Bax, SOX9, MDA, LDH, TNF-α and IL-6 were increased in the H/R group, and expression of Bcl-2, SOD and miR-138-5p were decreased (P < 0.05). Compared with the H/R group, cell proliferation viability, apoptosis rate, Bax, SOX9, MDA, LDH, TNF-α and IL-6 expression were decreased in the H/R+Dex group, and Bcl-2, SOD and miR-138-5p expression were increased in the H/R+Dex group (P < 0. 001). Compared with the H/R+Vector group, cell proliferation viability, apoptosis rate, Bax, SOX9, MDA, LDH, TNF-α and IL-6 expression were decreased in the H/R+miR-138-5p group, and Bcl-2, SOD and miR-138-5p expression were increased (P < 0.05). The expression of SOX9 in H/R+miR-138-5p group was lower than that in the H/R+Vector group (P < 0.001). Compared with WT-SOX9+Vector group, the expression level of SOX9 in WT-SOX9+miR-138-5p group was decreased (P < 0.05). There was no significant difference in the expression of SOX9 between the MUT-SOX9 +Vector group and the MUT- SOX9 +miR-138-5p group (P>0.05).
Conclusion
Dex inhibits the expression of SOX9 by up-regulating the expression level of miR-138-5p, alleviates inflammatory response and oxidative stress response, thereby alleviating the degree of myocardial cell damage caused by H/R.

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References (22)

References

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Protective effect and mechanism of dexmedetomidine on hypoxia-reoxygenated myocardial cells