Farrerol attenuates myocardial injury in sepsis-induced cardiomyopathy mice by inhibiting ferroptosis through Nrf2/HO-1 signaling pathway
10.3969/j.issn.1000-4718.2025.07.011
- VernacularTitle:杜鹃素通过Nrf2/HO-1通路抑制铁死亡减轻脓毒症心肌病小鼠的心肌损伤
- Author:
Yan DUAN
1
;
Jingyi WU
;
Baosong HAN
;
Xia ZHANG
Author Information
1. 皖南医学院第一附属医院超声科,安徽 芜湖 241001
- Publication Type:Journal Article
- Keywords:
sepsis-induced cardiomyopathy;
farrerol;
ferroptosis;
Nrf2/HO-1 signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(7):1345-1353
- CountryChina
- Language:Chinese
-
Abstract:
AIM:The current study aims to investigate the protective effect of farrerol against sepsis-induced cardiomyopathy and its mechanisms in mice.METHODS:Eighteen male C57BL/6 mice were randomly divided into the control,lipopolysaccharide(LPS;10 mg/kg),and LPS+farrerol(40 mg/kg)groups,with 6 mice in each group.The car-diac function of the mice was assessed via ultrasonography.Myocardial pathological changes and mitochondrial damage were examined via hematoxylin and eosin staining and transmission electron microscopy,respectively.TUNEL staining was performed to evaluate myocardial apoptosis,and RT-qPCR and ELISA were conducted to assess cardiac tissue inflam-matory factor mRNA expression and the serum inflammatory factor levels.Furthermore,the malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),Fe2+,and reactive oxygen species(ROS)levels in the myocardial tis-sues were evaluated using kits and immunofluorescence.Western blot analysis was performed to investigate the levels of key proteins associated with apoptosis,ferroptosis,and the nuclear factor E2-related facor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.RESULTS:Farrerol pretreatment prevented the reduction of cardiac function in mice with SIC(P<0.01).Further,it decreased myocardial tissue pathological damage,mitochondrial ultrastructural disruption,the inflammatory factor levels(P<0.01),cardiac oxidative stress and Fe2+content(P<0.01),the expression of apoptotic cardiomyocytes(P<0.01),and the level of Bax expression(P<0.01).Finally,it increased the protein expression of Bcl-2,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and HO-1(P<0.05 or P<0.01).The control,LPS,and LPS+farrerol groups did not significantly differ in terms of left ventricular anterior wall end-diastolic depth and left ventricular posterior wall end-diastolic depth(P>0.05).CONCLUSION:Farrerol reduces LPS-induced septic myocardial injury and inhibits the development of ferroptosis in the myocardial tissues of mice,which may be related to the Nrf2/HO-1 signaling pathway.
