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Article Open Access

Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway

  • Authors:
    • Yan Qu
    • Wei Xiong
    • Rui Zhou
    • Ning Song
    • Jinqiao Qian
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
    Copyright: © Qu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 251
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    Published online on: July 8, 2025
       https://doi.org/10.3892/mmr.2025.13616
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Abstract

Dexmedetomidine (Dex) is a selective α2‑adrenergic receptor agonist used for its sedative effects in anesthesia and critical care. Although Dex exhibits cardioprotective effects, to the best of our knowledge, the mechanisms underlying these effects, particularly in a high‑glucose (HG) environment, remain unclear. Research into the role of Dex in alleviating oxidative stress injury in cardiac myoblasts through the PI3K/AKT signaling pathway may reveal novel cardioprotective mechanisms, enhance the understanding of cell survival and metabolic regulation, and offer potential clinical applications in cardiac surgery and critical care. The aim of the present study was to assess the protective effect and mechanism of Dex preconditioning (DP) against hydrogen peroxide (H2O2)‑induced H9C2 cardiac myoblast injury under HG conditions. H9C2 cardiac myoblasts were either untreated or pretreated with 10 nM Dex and the PI3K inhibitor LY294002 before exposure to H2O2 to induce oxidative cellular damage in the presence of HG culture medium. Cell viability assays were carried out, and apoptosis was evaluated using flow cytometry, TUNEL assays and western blotting. Additionally, the relative levels of oxidative stress indicators, including superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA), were determined. Exposure to H2O2 significantly decreased cell viability and increased apoptosis in H9C2 cardiac myoblasts cultured in HG conditions. Treatment with Dex significantly mitigated H2O2‑induced apoptosis, as evidenced by reduced expression of caspase‑3 and BAX, and increased levels of BCL‑2. In addition, oxidative stress was elevated in the HG + H2O2 group, as indicated by increased levels of the oxidative stress marker MDA, and reduced levels of the antioxidant enzymes SOD and CAT compared with those in the HG group. By contrast, DP in the DP + HG + H2O2 group reduced MDA levels, and increased SOD and CAT levels, indicating improved oxidative stress regulation. Treatment with the PI3K/AKT inhibitor LY294002 in the LY294002 + HG + DP + H2O2 group prevented these effects, further increasing MDA levels, and decreasing SOD and CAT levels compared with the DP + HG + H2O2 group, suggesting that the protective effects of Dex were abrogated by inhibition of the PI3K/AKT pathway. The present study revealed that Dex pretreatment attenuated H9C2 cardiac myoblast injury via the PI3K/AKT signaling pathway under HG conditions. Its protective effects may be achieved by reducing oxidative stress damage to cardiac myoblasts.
View Figures

Figure 1

Cell experiment protocol. H9C2 cells
were cultured overnight in plates and divided into the following
four groups (n=5 wells/group): i) HG group: H9C2 cells were
cultured in DMEM containing 33 mM glucose for 490 min; ii) HG +
H2O2 group: H9C2 cells were cultured in DMEM
containing 33 mM glucose for 130 min, then treated with 600 µM
H2O2 for 360 min; iii) DP + HG +
H2O2 group: H9C2 cells were cultured in DMEM
containing 33 mM glucose, pretreated with 10 nM Dex for 120 min and
then treated with 600 µM H2O2 for 360 min;
and iv) LY + HG + DP + H2O2 group: H9C2 cells
were cultured in DMEM containing 33 mM glucose, treated with 10 µM
LY for 10 min, then treated with 10 nM Dex for 120 min and finally
treated with 600 µM H2O2 for 360 min. HG,
high-glucose; Dex, dexmedetomidine; DP, dexmedetomidine
preconditioning; H2O2, hydrogen peroxide; LY,
LY294002.

Figure 2

Cell viability was assessed using a
Cell Counting Kit-8 assay. Data are presented as the mean ± SEM;
n=5 per group. **P<0.01. HG, high-glucose; DP, dexmedetomidine
preconditioning; H2O2, hydrogen peroxide.

Figure 3

TUNEL staining analysis. (A)
Morphological changes were detected by TUNEL staining
(magnification, ×40). (B) Quantification of TUNEL staining. Data
are presented as the mean ± SEM; n=5 per group. **P<0.01. HG,
high-glucose; DP, dexmedetomidine preconditioning;
H2O2, hydrogen peroxide.

Figure 4

Flow cytometry analysis of apoptosis.
(A) HG group. (B) HG + H2O2 group. (C) DP +
HG + H2O2 group. (D) LY294002 + HG + DP +
H2O2 group. (E) Quantification of H9C2 cell
apoptosis. **P<0.01. Data are presented as the mean ± SEM, n=5
per group. HG, high-glucose; DP, dexmedetomidine preconditioning;
H2O2, hydrogen peroxide.

Figure 5

Detection of the levels of
apoptosis-related proteins by western blotting. (A) Protein bands
of apoptosis-related proteins caspase-3, PI3K, AKT, BCL-2, BAX,
p-PI3K and p-AKT in H9C2 cells from the four groups assessed by
western blotting. GAPDH served as an internal control for sample
loading. The differing band curvatures observed (‘frown’ effect for
p-PI3K and ‘smile’ effect for t-PI3K) may result from minor
membrane handling variations during blotting or localized gel
inconsistencies during protein migration. These factors cause
uneven stretching, folding or pressure, leading to the observed
discrepancies. Semi-quantification of western blotting data of
apoptosis-related proteins, including (B) caspase-3, (C) BCL-2, (D)
BAX, (E) p/t-PI3K and (F) p/t-AKT, in H9C2 cells from the four
groups. n=3 per group. *P<0.05, **P<0.01. HG, high-glucose;
Dex, dexmedetomidine; DP, dexmedetomidine preconditioning; p,
phosphorylated; t, total; H2O2, hydrogen
peroxide.

Figure 6

Analysis of oxidative stress markers
in each group. (A) SOD), (B) Catalase (CAT), and (C)
Malondialdehyde (MDA). Data are presented as the mean ± SEM; n=5
per group. **P<0.01, SOD, superoxide dismutase; CAT, catalase;
MDA, malondialdehyde; HG, high-glucose; DP, dexmedetomidine
preconditioning; H2O2, hydrogen peroxide;
mgprot, mg protein.
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Copy and paste a formatted citation
Spandidos Publications style
Qu Y, Xiong W, Zhou R, Song N and Qian J: Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway. Mol Med Rep 32: 251, 2025.
APA
Qu, Y., Xiong, W., Zhou, R., Song, N., & Qian, J. (2025). Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway. Molecular Medicine Reports, 32, 251. https://doi.org/10.3892/mmr.2025.13616
MLA
Qu, Y., Xiong, W., Zhou, R., Song, N., Qian, J."Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway". Molecular Medicine Reports 32.3 (2025): 251.
Chicago
Qu, Y., Xiong, W., Zhou, R., Song, N., Qian, J."Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway". Molecular Medicine Reports 32, no. 3 (2025): 251. https://doi.org/10.3892/mmr.2025.13616
Copy and paste a formatted citation
x
Spandidos Publications style
Qu Y, Xiong W, Zhou R, Song N and Qian J: Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway. Mol Med Rep 32: 251, 2025.
APA
Qu, Y., Xiong, W., Zhou, R., Song, N., & Qian, J. (2025). Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway. Molecular Medicine Reports, 32, 251. https://doi.org/10.3892/mmr.2025.13616
MLA
Qu, Y., Xiong, W., Zhou, R., Song, N., Qian, J."Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway". Molecular Medicine Reports 32.3 (2025): 251.
Chicago
Qu, Y., Xiong, W., Zhou, R., Song, N., Qian, J."Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway". Molecular Medicine Reports 32, no. 3 (2025): 251. https://doi.org/10.3892/mmr.2025.13616
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