Relationship between high-glucose-induced attenuation of cardioprotective effect of sevoflurane postconditioning and HIF-1α/MCT4 signaling pathway: a cell-based experiment
10.3760/cma.j.cn131073-20250120-01109
- VernacularTitle:高糖因素减弱七氟烷后处理心肌保护效应与HIF-1α/MCT4信号通路的关系：细胞实验
- Author:
Tianliang HOU
1
;
Long YANG
;
Haiping MA
;
Talaiti ALAITI·
;
Jiang WANG
Author Information
1. 新疆医科大学第一附属医院麻醉科，乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus;
Myocardial reperfusion injury;
Sevoflurane;
Hypoxia-indu-cible factor 1, alpha subunit;
Monocarboxylic acid transporters
- From:
Chinese Journal of Anesthesiology
2025;45(11):1433-1438
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate whether the mechanism by which high glucose attenuated the cardioprotective effect of sevoflurane postconditioning was associated with the hypoxia-inducible factor-1α (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling pathway in rat cardiomyocytes.Methods:H9C2 cardiomyocytes were cultured at a 1∶4 ratio and then divided into 8 groups ( n=21 each) using a table of random numbers: control group (N+ Con group), hypoxia-reoxygenation (H/R) group (N+ H/R group), sevoflurane postconditioning group (N+ SPostC group), high glucose control group (H+ Con group), high glucose-H/R group (H+ H/R group), high glucose sevoflurane postconditioning group (H+ SPostC group), high glucose sevoflurane postconditioning + HIF-1α agonist group (H+ SPostC+ D group), and high glucose sevoflurane postconditioning + HIF-1α agonist + MCT4 inhibitor group (H+ SPostC+ D+ A group). N+ Con, N+ H/R and N+ SPostC groups were cultured in conventional culture dishes, while high-glucose group was incubated in high-glucose (35 mmol/L) DMEM. Cells were subjected to 3 h of hypoxia in serum-free and glucose-free DMEM using a three-gas incubator, followed by 3 h of reoxygenation in fresh DMEM in a CO 2 incubator. Sevoflurane postconditioning was performed as follows: Cells were incubated at 37 ℃ in a three-gas incubator filled with sevoflurane (2.4%) for 15 min. At 2 h before hypoxia, H+ SPostC+ D group was incubated in medium containing 1 mmol/L DMOG (HIF-1α agonist), and H+ SPostC+ D+ A group was incubated in medium containing 1 mmol/L DMOG and 10 μmol/L AZD0095 (MCT4 inhibitor). The viability of cardiomyocytes (by CCK8 assay), levels of LDH in culture medium (by microplate assay), levels of lactate (by WST-8 assay), levels of ATP (by chemiluminescence assay), apoptosis rate of cells (by flow cytometry), mitochondrial membrane potential (by fluorescence probe assay), and expression of HIF-1α and MCT4 (by Western blot) were measured. Results:Compared with N+ H/R group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in N+ SPostC group ( P<0.05). There were no significant differences in each parameter between H+ H/R group and H+ SPostC group ( P>0.05). Compared with H+ SPostC group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in H+ SPostC+ D group ( P<0.05). Compared with H+ SPostC+ D group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly decreased, the levels of LDH in culture medium and apoptosis rates of cells were increased, and the expression of HIF-1α and MCT4 was down-regulated in H+ SPostC+ D+ A group ( P<0.05). Conclusions:The mechanism by which high glucose attenuates the cardioprotective effect of sevoflurane postconditioning may be related to the inhibition of the HIF-1α/MCT4 signaling pathway in rat cardiomyocytes.
