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| Mechanism of Tongmai Yangxin Prescription in ameliorating hypoxia/reoxygenation-induced cardiomyocyte injury via the MFN2/PERK signaling pathway |
| Hits 61 Download times 31 Received:April 25, 2026 |
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| DOI
10.11656/j.issn.1672-1519.2026.07.11 |
| Key Words
Tongmai Yangxin Prescription;mitochondria;hypoxia/reoxygenation;apoptosis;MFN2/PERK signaling pathwa |
| Author Name | Affiliation | E-mail | | LIU Shu | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | LIU Yutong | Beijing University of Chinese Medicine Dongfang Hospital Qinhuangdao Branch(Qinhuangdao Traditional Chinese Medicine Hospital), Qinhuangdao 066000, China | | | YU Lu | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | YU Chunquan | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | ycqtjutcm@foxmail.com | | LI Lin | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | llbianji@163.com |
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| Abstract
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| [Objective] The Tongmai Yangxin Prescription is widely used in clinical practice to treat angina pectoris in coronary heart disease. This study aims to investigate the mechanism by which Tongmai Yangxin Prescription ameliorates hypoxia/reoxygenation（H/R）-induced injury in cardiomyocytes，focusing on the regulation of the mitofusin 2/protein kinase R-like ER kinase（MFN2/PERK） signaling pathway. [Methods] Various concentrations of Tongmai Yangxin Prescription extract were prepared in advance. An H/R model was established using H9c2 cardiomyocytes，and the optimal concentration of Tongmai Yangxin Prescription ethanolic extract was determined by the MTT assay. Mitochondrial morphology was examined using transmission electron microscopy（TEM）and MitoTracker probes. Changes in mitochondrial membrane potential were assessed by JC-1 staining. Mitochondrial energy metabolism was evaluated by measuring adenosine triphosphate（ATP）levels. Mitochondrial respiratory function was analyzed using a Seahorse XF Analyzer. Intracellular reactive oxygen species（ROS）levels were detected with the fluorescent probe DCFH-DA. The mRNA and protein expression of key genes in the MFN2/PERK pathway and apoptosis-related factors were measured by quantitative real-time PCR （qPCR）and Western blot analysis，respectively. [Results] The results demonstrated that，compared with the model group，treatment with Tongmai Yangxin Prescription significantly ameliorated H/R injury in H9c2 cardiomyocytes. Specifically，Tongmai Yangxin Prescription administration reduced intracellular ROS levels，attenuated mitochondrial structural damage，increased ATP content，and elevated the mitochondrial membrane potential. Furthermore，it enhanced mitochondrial respiratory function，as evidenced by increased basal respiration，maximal respiration，and ATP-linked oxygen consumption rate. At the molecular level，Tongmai Yangxin Prescription up-regulated the mRNA and protein expression of Mfn2 and Bcl-2，while down-regulating the expression of key mediators in the PERK pathway（PERK，eIF2α，ATF4，and CHOP）and pro-apoptotic factors（Bax and Cleaved Caspase-3）. These beneficial effects were observed in a dose-dependent manner，with the most pronounced outcomes in the high-dose Tongmai Yangxin Prescription group. [Conclusion] These findings suggest that Tongmai Yangxin Prescription confers protective effects against mitochondrial injury in cardiomyocytes，potentially through the modulation of the MFN2/PERK signaling pathway. |
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