海南医科大学学报2026，Vol.32Issue(9)：687-696,10.DOI:10.13210/j.cnki.jhmu.20250227.002
五味子乙素通过抑制Nrf2/GPX4通路介导的铁死亡减轻脓毒症小鼠心肌损伤
Mechanistic study of Schisandrin B alleviating myocardial injury in septic mice by inhibiting ferroptosis via activation of the Nrf2/GPX4 axis
摘要
Abstract
Objective:To explore the protective effect of Schisandrin B(Sch B)on sepsis-induced myocardial dysfunction(SIMD)and its specific mechanism of action.Methods:A total of thirty male C57BL/6J mice were randomly divided into the con-trol group(CON group),the Sepsis group(10 mg/kg LPS group),the LPS+Sch B with low-dose administration(20 mg/kg)group(Sch B-L group),the LPS+Sch B with high-dose administration(40 mg/kg)group(Sch B-H group)and the LPS+Sch B(40 mg/kg)+Nrf2 inhibitor ML385(30 mg/kg)group(ML385 group),with 6 mice in each group,and were treated by intraperi-toneal injection of LPS to construct the sepsis mouse model.All mice underwent cardiac ultrasonography 24 h after modelling,fol-lowed by heart sampling and collection of relevant samples.H&E staining was used to evaluate the pathological tissue changes in myocardial tissues of mice,ELISA was used to detect the levels of serum CK-MB,cTnI,IL-1β,and TNF-α;and relevant kits were used to determine the levels of MDA,GSH,SOD,and Fe2+in myocardial tissues;and immunohistochemistry,Western blotting,and RT-qPCR were used to detect the expression of GPX4,Nrf2,SLC7A11,FTH1,ACSL4 in tissues.Results:Compared to the CON group,LVEF and LVFS in the LPS group were significantly lower,the levels of CK-MB,cTnI,IL-1β,and TNF-α were significantly increased;and disturbed arrangement of cardiomyocytes,widening of intra-tissue gaps,oedema,and a higher inflammatory cell infiltration could be observed in H&E staining.In contrast,mice pretreated with Sch B did not show obvious myocardial injury,and the levels of MDA and Fe2+in myocardial tissues were reduced,the levels of GSH and SOD were increased,the protein expression of GPX4,SLC7A11,Nrf2 and FTH1,and the mRNA content of GPX4 and SLC7A11 were in-creased,and the level of ACSL4 was decreased compared to that of the LPS group.The Nrf2 inhibitor group reversed the protec-tive effect of Schisandra chinensis ethanol and aggravated the degree of cardiomyocyte injury and ferroptosis compared to the Chi-nese medicine group.Conclusion:Schisandrin B alleviated LPS-induced myocardial dysfunction in mice by attenuating ferropto-sis,and its mechanism may be related to the activation of Nrf2/GPX4 pathway.关键词
五味子乙素/脓毒症心肌损伤/铁死亡/核因子E2相关因子2(Nrf2)/谷胱甘肽过氧化酶4(GPX4)Key words
Schisandrin B/Sepsis-induced myocardial injury/Ferroptosis/Nuclear factor E2 related factor 2(Nrf2)/Gluta-thione peroxidase 4(GPX4)分类
医药卫生引用本文复制引用
王磬妍,孙凤霄,张敬,董波..五味子乙素通过抑制Nrf2/GPX4通路介导的铁死亡减轻脓毒症小鼠心肌损伤[J].海南医科大学学报,2026,32(9):687-696,10.基金项目
This study was supported by the National Natural Science Foundation of China(82070382) （82070382）
Shandong Province Taishan Scholar Fund(ts20190979) 国家自然科学基金(82070382) （ts20190979）
山东省泰山学者基金(ts20190979) （ts20190979）
