Inhibiting ferroptosis attenuates myocardial injury in septic mice: the role of lipocalin-2 / 南方医科大学学报
Journal of Southern Medical University
; (12): 256-262, 2022.
Article
de Zh
| WPRIM
| ID: wpr-936310
Bibliothèque responsable:
WPRO
ABSTRACT
OBJECTIVE@#To explore the contribution of ferroptosis to myocardial injury in mouse models of sepsis and the role lipocalin-2 (Lcn2) in ferroptosis.@*METHODS@#Adult male C57BL/6 mice were randomized equally into sham-operated group, cecal ligation and puncture (CLP)-induced sepsis group, and CLP + Fer-1 group where the mice received intraperitoneal injection of 5 mg/mL Fer-1 (5 mg/kg) 1 h before CLP. The left ventricular functions (including LVEF%, LVFS%, LVIDd and LVIDs) of the mice were assessed by echocardiography at 24 h after CLP. Myocardial injury in the mice was observed with HE staining, and the changes of myocardial ultrastructure and mitochondria were observed using transmission electron microscopy (TEM). Serum TNF-α level was measured with ELISA, and the changes of myocardial iron content were detected using tissue iron kit. The protein expressions of myocardial Lcn2, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) were determined with Western blotting.@*RESULTS@#The septic mice showed significantly decreased LVEF%, LVFS% and LVIDd and increased LVIDs at 24 h after CLP (P < 0.05), and these changes were significantly improved by Fer-1 treatment. Sepsis caused obvious myocardial pathologies and changes in myocardial ultrastructure and mitochondria, which were significantly improved by Fer-1 treatment. Fer-1 treatment also significantly ameliorated sepsis-induced elevations of serum TNF-α level, myocardial tissue iron content, and Lcn2 protein expression and the reduction of GPX4 and FSP1 protein expression levels (P < 0.05).@*CONCLUSION@#GPX4- and FSP1-mediated ferroptosis are involved in myocardial injury in mice with CLP-induced sepsis, and inhibition of ferroptosis can attenuate septic myocardial injury, in which Lcn2 may play a role.
Mots clés
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Sepsie
/
Lipocaline-2
/
Ferroptose
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Lésions traumatiques du coeur
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Souris de lignée C57BL
Limites du sujet:
Animals
langue:
Zh
Texte intégral:
Journal of Southern Medical University
Année:
2022
Type:
Article