The protective effect of Iron Isomaltoside on myocardial ischemia-reperfusion injury via the suppression of KLF4/NF-κB signaling

Author:

Gong Huiping1,Zhao Qingyang1,Zhang Jingbo1,Sun Duanchen2,Zhuang Xianghua1,Dong Qiaofeng3,Dou Aixia1

Affiliation:

1. Second Hospital of Shandong University

2. School of Mathematics, Shandong University

3. Department of Haematology,Heze Municipal hospital

Abstract

Abstract

[Objectives] 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. [Design & Methods] Changes in cardiac pathology after myocardial infarction (MI) were analyzed with hematoxylin-eosin staining. Myocardial cellapoptosis 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. [Results] 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. [Conclusions] 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.

Publisher

Research Square Platform LLC

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