GPX4
脂质过氧化
药理学
下调和上调
心力衰竭
医学
程序性细胞死亡
败血症
心肌病
化学
氧化应激
细胞凋亡
内科学
生物化学
过氧化氢酶
谷胱甘肽过氧化物酶
基因
作者
Liying Guo,Jie Li,Yuming Wang,Jing Wang,Jinyan Lei,Jie Zhao,WU Xi-liang,Wenju He,Jianwei Jia,Jing Miao,Dongqiang Wang,Huantian Cui
出处
期刊:Shock
[Ovid Technologies (Wolters Kluwer)]
日期:2023-11-15
卷期号:61 (4): 638-645
被引量:1
标识
DOI:10.1097/shk.0000000000002257
摘要
Sepsis-induced cardiomyopathy ( SIC ) is a distinct form of myocardial injury that disrupts tissue perfusion and stands as the significant cause of mortality among sepsis patients. Currently, effective preventive or treatment strategies for SIC are lacking. YiQiFuMai injection (YQFM), composed of Panax ginseng C.A. Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., is widely used in China to treat cardiovascular diseases, such as coronary heart disease, heart failure, and SIC . Research has shown that YQFM can improve cardiac function and alleviate heart failure through multiple pathways. Nevertheless, the mechanisms through which YQFM exerts its effects on SIC remain to be fully elucidated. In this study, we firstly investigated the therapeutic effects of YQFM on a SIC rat model and explored its effects on myocardial ferroptosis in vivo. Then, LPS-induced myocardial cell death model was used to evaluate the effects of YQFM on ferroptosis and xCT/GPX4 axis in vitro . Furthermore, using GPX4 inhibitors, we aimed to verify whether YQFM improved cardiomyocyte ferroptosis through the xCT/GPX4 axis. The results showed that YQFM was effective in alleviating myocardial injury in septic model rats. Besides, the concentrations of iron and the levels of lipid peroxidation-related factors (ROS, MDA, and 4-HNE) were significantly decreased and the expression of xCT/GPX4 axis was upregulated in SIC rats after YQFM treatment. In vitro studies also showed that YQFM alleviated iron overload and lipid peroxidation and activated xCT/GPX4 axis in LPS-induced myocardial cell death model. Moreover, GPX4 inhibitor could abolish the effects above. In summary, the study highlights the regulatory effect of YQFM in mitigating myocardial injury. It probably achieves this ameliorative effect by enhancing xCT/GPX4 axis and further reducing ferroptosis.
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