天津中医药2026，Vol.43Issue(8)：1009-1016,8.DOI:10.11656/j.issn.1672-1519.2026.08.09
基于GAS6/Axl通路探讨茯苓酸预处理对过氧化氢诱导的心肌细胞损伤的影响
Exploring the effect of pachymic acid pretreatment on hydrogen peroxide-induced cardiomyocyte damage based on the GAS6/Axl pathway
摘要
Abstract
[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 by 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 by 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.关键词
茯苓酸/GAS6/Axl通路/过氧化氢/心肌细胞损伤Key words
pachymic acid/GAS6/Axl pathway/hydrogen peroxide/cardiomyocyte damage分类
医药卫生引用本文复制引用
张晓娟,刘沙沙,刘影,程丽,宋燕齐,李春玲..基于GAS6/Axl通路探讨茯苓酸预处理对过氧化氢诱导的心肌细胞损伤的影响[J].天津中医药,2026,43(8):1009-1016,8.基金项目
河北省医学科学研究课题(20261384). （20261384）
