Curcumin alleviates septic lung injury in mice by inhibiting TXNIP/TRX-1/GPX4-mediated ferroptosis
10.12122/j.issn.1673-4254.2024.09.21
- VernacularTitle:姜黄素通过抑制TXNIP/TRX-1/GPX4通路介导的铁死亡减轻脓毒症小鼠肺损伤
- Author:
Kai CHEN
1
;
Zhaofei MENG
;
Jingting MIN
;
Jiahui WANG
;
Zhenghong LI
;
Qin GAO
;
Junfeng HU
Author Information
1. 蚌埠医科大学第一附属医院呼吸与危重症医学科,安徽 蚌埠 233000
- Keywords:
sepsis lung injury;
curcumin;
ferroptosis;
TXNIP/TRX-1/GPX4 pathway
- From:
Journal of Southern Medical University
2024;44(9):1805-1813
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.
