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| Exploring the effect of pachymic acid pretreatment on hydrogen peroxide-induced cardiomyocyte damage based on the GAS6/Axl pathway |
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| DOI
10.11656/j.issn.1672-1519.2026.08.09 |
| Key Words
pachymic acid;GAS6/Axl pathway;hydrogen peroxide;cardiomyocyte damage |
| Author Name | Affiliation | E-mail | | ZHANG Xiaojuan | Department of Pharmacy, Handan Hospital of Integrated Traditional Chinese and Western Medicine, Handan 056000, China | | | LIU Shasha | The Fifth Department of Cardiology, Baoding No. 1 Central Hospital, Baoding 071000, China | dhbjpn@163.com | | LIU Ying | Department of Integrated Traditional Chinese and Western Medicine, The Eighth People's Hospital of Hebei Province, Shijiazhuang 050000, China | | | CHENG Li | Department of Pharmacy, Handan Hospital of Integrated Traditional Chinese and Western Medicine, Handan 056000, China | | | SONG Yanqi | Department of Pharmacy, Handan Hospital of Integrated Traditional Chinese and Western Medicine, Handan 056000, China | | | LI Chunling | Department of Pharmacy, Handan Hospital of Integrated Traditional Chinese and Western Medicine, Handan 056000, China | |
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| Abstract
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| Objective To investigate the effect of pachymic acid (PA) pretreatment on oxidative damage of rat cardiomyocytes H9c2 induced by hydrogen peroxide (H2O2), and to clarify its potential mechanism based on the growth arrest specific protein 6/tyrosine protein kinase receptor (GAS6/Axl) signaling pathway. Methods H9c2 cells and H9c2 cells induced b H2O2 were treated with different concentrations of pachymic acid (0 to 40 μmol/L), and the optimal experimental drug concentration of pachymic acid was screened by the CCK-8 method. H9c2 cells were assigned into: the control group (CN group), the H2O2 group, the low, medium and high concentration pachymic acid groups (PA-L group, PA-M group, PA-H group, 2.50, 5.00, 10.00 μmol/L), and the high concentration pachymic acid+GAS6/Axl pathway inhibitor group (PA-H+R428 group). Cell apoptosis was detected by TUNEL staining. The expressions of apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Cleaved-Caspase-3, Caspase-3) ]and GAS6/Axl pathway proteins (GAS6, p-Axl, Axl) were measured by Western blot. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were detected using the corresponding kits. Results Compared with the CN group, H2O2 treatment could induce severe oxidative damage to H9c2 cells, manifested as deterioration of cell survival rate and morphology, a prominent increase in apoptosis rate (P < 0.05), the decreases of Bcl-2/Bax ratio and the activities of SOD and GSH-Px (P < 0.05), and the increases of Cleaved-Caspase-3/Caspase-3 ratio and the levels of MDA and ROS (P < 0.05), while the GAS6/Axl pathway was prominently inhibited (P < 0.05). Pachymic acid pretreatment could reverse the above-mentioned injuries in a concentration-dependent manner, and among them, the PA-H group had the most prominent effect, and all indicators were close to the normal level. However, after the addition of the GAS6/Axl pathway-specific inhibitor R428, the protective effect of pachymic acid was prominently weakened (P < 0.05). Conclusion Pachymic acid pretreatment can effectively alleviate oxidative damage and apoptosis of H9c2 cardiomyocytes induced b H2O2. Its mechanism of action may be related to the activation of the GAS6/Axl signaling pathway, thereby enhancing the antioxidant capacity of cells and regulating the expression of apoptosis-related proteins. |
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