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Dexmedetomidine reversed hypoxia/reoxygenation injury-induced oxidative stress and endoplasmic reticulum stress-dependent apoptosis of cardiomyocytes via SIRT1/CHOP signaling pathway

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We aimed to investigate the protective role and mechanism of dexmedetomidine (DEX) on H9c2 cardiomyocytes after hypoxia/reoxygenation (H/R) injury. Six experimental groups were designed as follows: normal control group (group C), H/R group, H/R + DEX group, H/R + gastrodin group, H/R + Ex527 (SIRT1 inhibitor) group, and H/R + DEX + Ex527 group. Lactate dehydrogenase (LDH) activity and the levels of oxidative stress-related enzymes such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured using corresponding commercial kits. Cell counting kit (CCK)-8 assay was used to detect cell survival rate while flow cytometry and caspase 3/7 activity were used to determine cell apoptosis, respectively. Western blot was used to detect the expression of silent information regulator 1 (SIRT1), C/EBP homologous protein (CHOP), cleaved-caspase-12/3 and pro-caspase-12/3 in each group. From our findings, when compared with H/R, H/R + Ex527 and H/R + DEX + Ex527 groups, DEX pretreatment of cells in H/R + DEX group significantly increased cell survival rate, and simultaneously reduced LDH activity, oxidative stress and the apoptosis rate of H9c2 cells with H/R injury. Moreover, DEX up-regulated SIRT1 expression level and down-regulated the levels of endoplasmic reticulum (ER) stress-related markers such as CHOP, cleaved-caspase-12 and cleaved-caspase-3, respectively. Ex527 could completely block DEX-induced upregulated expression of SIRT1, and partially blocked the DEX-induced downregulated expression levels of CHOP, cleaved-caspase-12 and cleaved-caspase-3. These results proved that DEX reversed H/R injury-induced oxidative stress and ER stress-dependent apoptosis of cardiomyocytes via SIRT1/CHOP signaling pathway.

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Funding

This work was supported by the Natural Science Research Foundation of Department of Education in Anhui Province (KJ2019A0388).

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou, 215006, Jiangsu Province, China

    Ying Zhang & Fuhai Ji

  2. Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China

    Ying Zhang & Xiaohong Li

  3. Department of Anesthesiology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China

    Qihong Zhao

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  1. Ying Zhang
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FJ conceptualized and designed the study. YZ wrote the paper. YZ, QZ and XL performed research and analyzed data. All authors have read and approved the final version of manuscript.

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Correspondence to Fuhai Ji.

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Zhang, Y., Zhao, Q., Li, X. et al. Dexmedetomidine reversed hypoxia/reoxygenation injury-induced oxidative stress and endoplasmic reticulum stress-dependent apoptosis of cardiomyocytes via SIRT1/CHOP signaling pathway. Mol Cell Biochem 476, 2803–2812 (2021). https://doi.org/10.1007/s11010-021-04102-8

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