南方医科大学学报2024，Vol.44Issue(1)：166-172,7.DOI:10.12122/j.issn.1673-4254.2024.01.19
亚精胺通过抑制细胞凋亡、ROS生成及铁死亡减轻脂多糖诱导的小鼠心肌损伤
Spermidine alleviates lipopolysaccharide-induced myocardial injury in mice by suppressing apoptosis,ROS production and ferroptosis
摘要
Abstract
Objective To investigate the protective effect of spermidine against lipopolysaccharide(LPS)-induced myocardial injury in mice and the underlying mechanism.Methods C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy.In the cell experiment,cultured rat cardiomyocytes(H9c2 cells)were pretreated with 10 or 20 μmol/L spermidine before LPS exposure for 2 h,and the changes in cell viability and levels of lactate dehydrogenase(LDH)and cardiac troponin Ⅰ(cTNI)were assessed using CCK-8 kit,LDH detection kit and ELISA,respectively.Western blotting was performed to detect the changes in the expressions of Bax,Bcl-2,cleaved caspase-3,SLC7A11 and GPX4;the changes in reactive oxygen species(ROS)and Fe2+ levels were detected using fluorescent probes,and mitochondrial membrane potential of the cells was measured using JC-1 staining.Results Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages,which were significantly alleviated by pretreatment with spermidine.In H9c2 cells,LPS exposure significantly lowered the cell viability,increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels,decreased expressions of Bcl-2,SLC7A11 and GPX4,increased ROS production and Fe2+ level(P<0.05),and lowered mitochondrial membrane potential(all P<0.05).These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure.Conclusion Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.关键词
脓毒症/脂多糖/心肌损伤/亚精胺/铁死亡Key words
sepsis/lipopolysaccharide/myocardial injury/spermidine/ferroptosis引用本文复制引用
张晓红,赵品,蒯建科,常超,袁庆..亚精胺通过抑制细胞凋亡、ROS生成及铁死亡减轻脂多糖诱导的小鼠心肌损伤[J].南方医科大学学报,2024,44(1):166-172,7.基金项目
陕西省自然科学基金(2023-JC-QN-0938) （2023-JC-QN-0938）
陕西省科研基金(2018SF-095) （2018SF-095）
西安市卫健委项目(2020qn09) （2020qn09）
