Gong Huiping, Zhao Qingyang, Zhang Jingbo, Sun Duanchen, Zhuang Xianghua, Dong Qiaofeng, Dou Aixia
Department of Emergency, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
Department of Cadres Medical Care/Gerontology Geriatric, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
PLoS One. 2025 Jun 5;20(6):e0323247. doi: 10.1371/journal.pone.0323247. eCollection 2025.
This study aimed to investigate the beneficial effects of iron isomaltoside (IIM) on myocardial function and the associated mechanisms in rats with myocardial ischemia/reperfusion (I/R)-induced damage and hypoxia/reoxygenation (H/R)-induced H9C2 cells. Changes in cardiac pathology after myocardial infarction (MI) were analyzed with hematoxylin-eosin staining. Myocardial cell apoptosis in the heart tissues of rats with MI was assessed using TUNEL staining. In H/R-induced H9C2 cells, cell viability and lactate dehydrogenase (LDH) and adenosine 5'-triphosphate levels were detected. Apoptosis and MMP in H9C2 cells were detected with flow cytometry. Our results demonstrated that IIM treatment reduced myocardial injury induced by ischemia-reperfusion (I/R) and suppressed cardiomyocyte apoptosis, inflammation, and autophagy induced by I/R in rats. Moreover, we confirmed that IIM repressed apoptosis and regulated MMP in H9C2 cells exposed to H/R. IIM relieved the inflammatory response and autophagy in H/R-treated H9C2 cells. In addition, IIM inhibited the Krüpple-like factor 4 (KLF4)/NF-κB pathway in H/R-induced H9C2 cells. Interestingly, the function of IIM on apoptosis, MMP, inflammation and autophagy were abolished by KLF4 overexpression in H/R-induced H9C2 cells. In conclusion, IIM could repress cardiomyocyte apoptosis, inflammation and autophagy through the inhibition of the KLF4/NF-κB pathway and thus reduced myocardial injury in vivo and in vitro.
本研究旨在探讨异麦芽糖铁（IIM）对心肌缺血/再灌注（I/R）诱导损伤的大鼠心肌功能及相关机制的有益作用，以及对缺氧/复氧（H/R）诱导的H9C2细胞的影响。采用苏木精-伊红染色分析心肌梗死后心脏病理变化。使用TUNEL染色评估心肌梗死大鼠心脏组织中的心肌细胞凋亡。在H/R诱导的H9C2细胞中，检测细胞活力、乳酸脱氢酶（LDH）和三磷酸腺苷水平。通过流式细胞术检测H9C2细胞中的凋亡和线粒体膜电位（MMP）。我们的结果表明，IIM治疗可减轻缺血再灌注（I/R）诱导的心肌损伤，并抑制I/R诱导的大鼠心肌细胞凋亡、炎症和自噬。此外，我们证实IIM可抑制暴露于H/R的H9C2细胞中的凋亡并调节MMP。IIM可减轻H/R处理的H9C2细胞中的炎症反应和自噬。此外，IIM可抑制H/R诱导的H9C2细胞中的Krüpple样因子4（KLF4）/核因子κB（NF-κB）信号通路。有趣的是，在H/R诱导的H9C2细胞中，KLF4过表达消除了IIM对凋亡、MMP、炎症和自噬的作用。总之，IIM可通过抑制KLF4/NF-κB信号通路抑制心肌细胞凋亡、炎症和自噬，从而减轻体内和体外的心肌损伤。
