Baicalin Prevents Myocardial Ischemia/Reperfusion Injury Through Inhibiting ACSL4 Mediated Ferroptosis

被引：172

作者：

Fan, Zhenyu ^{[1
]}

Cai, Liangliang ^{[1
]}

Wang, Shengnan ^{[1
]}

Wang, Jing ^{[1
]}

Chen, Bohua ^{[1
]}

机构：

[1] Nantong Univ, Affiliated Hosp, Dept Pharm, Nantong, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2021年 / 12卷

基金：

中国国家自然科学基金;

关键词：

baicalin; ferroptosis; acyl-CoA synthetase long-chain family member 4; myocardial; ischemia; reperfusion injury; ISCHEMIA-REPERFUSION INJURY; TRANSFERRIN RECEPTOR; AUTOPHAGY; MODEL; INFARCTION; APOPTOSIS; FERRITIN; EXERTS; MICE;

D O I：

10.3389/fphar.2021.628988

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Baicalin is a natural flavonoid glycoside that confers protection against myocardial ischemia/reperfusion (I/R) injury. However, its mechanism has not been fully understood. This study focused on elucidating the role of ferroptosis in baicalin-generated protective effects on myocardial ischemia/reperfusion (I/R) injury by using the myocardial I/R rat model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9c2 cells. Our results show that baicalin improved myocardial I/R challenge-induced ST segment elevation, coronary flow (CF), left ventricular systolic pressure , infarct area, and pathological changes and prevented OGD/R-triggered cell viability loss. In addition, enhanced lipid peroxidation and significant iron accumulation along with activated transferrin receptor protein 1 (TfR1) signal and nuclear receptor coactivator 4 (NCOA4)-medicated ferritinophagy were observed in in vivo and in vitro models, which were reversed by baicalin treatment. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) overexpression compromised baicalin-generated protective effect in H9c2 cells. Taken together, our findings suggest that baicalin prevents against myocardial ischemia/reperfusion injury via suppressing ACSL4-controlled ferroptosis. This study provides a novel target for the prevention of myocardial ischemia/reperfusion injury.

引用

页数：13

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