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Ferroptosis was involved in the oleic acid-induced acute lung injury in mice

ZHOU Hang^1,2, LI Feng^1,2, NIU Jian-Yi^1,2, ZHONG Wei-Yong^1,2, TANG Min-Yu^1,2, LIN Dong^1,2, CUI Hong-Hui^1,2, HUANG Xue-Han^1,2, CHEN Ying-Ying^1,3, WANG Hong-Yan⁴, TU Yong-Sheng^1,*

¹Department of Physiology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China；²The First Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China；³The Sixth Clinical Medical College, Guangzhou Medical University, Guangzhou 511436, China；⁴Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China

Abstract

The aim of the present study was to investigate the role of ferroptosis in acute lung injury (ALI) mouse model induced by oleic acid (OA). ALI was induced in the mice via the lateral tail vein injection of pure OA. The histopathological score of lung, lung wet-dry weight ratio and the protein content of bronchoalveolar lavage fluid (BALF) were used as the evaluation indexes of ALI. Iron concentration, glutathione (GSH) and malondialdehyde (MDA) contents in the lung tissues were measured using corresponding assay kits. The ultrastructure of pulmonary cells was observed by transmission electron microscope (TEM), and the expression level of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA was detected by quantitative polymerase chain reaction (q-PCR). Protein expression levels of glutathione peroxidase 4 (GPX4), ferritin and transferrin receptor 1 (TfR1) in lung tissues were determined by Western blot. The results showed  that histopathological scores of lung tissues, lung wet-dry weight ratio and protein in BALF in the OA group were higher than those of the control group. In the OA group, the mitochondria of pulmonary cells were shrunken, and the mitochondrial membrane was ruptured. The expression level of PTGS2 mRNA in the OA group was seven folds over that in the control group. Iron overload, GSH depletion and accumulation of MDA were observed in the OA group. Compared with the control group, the protein expression levels of GPX4 and ferritin in lung tissue were down-regulated in the OA group. These results suggest that ferroptosis plays a potential role in the pathogenesis of ALI in our mouse model, which may provide new insights for development of new drugs for ALI. 

Key words: acute lung injury; oleic acid; ferroptosis; glutathione; glutathione peroxidase 4; iron

Received: 2019-02-28　　Accepted: 2019-07-01

Corresponding author: 涂永生　　E-mail: tuys@gzhmu.edu.cn

DOI: 10.13294/j.aps.2019.0070

Citing This Article：

ZHOU Hang, LI Feng, NIU Jian-Yi, ZHONG Wei-Yong, TANG Min-Yu, LIN Dong, CUI Hong-Hui, HUANG Xue-Han, CHEN Ying-Ying, WANG Hong-Yan, TU Yong-Sheng. Ferroptosis was involved in the oleic acid-induced acute lung injury in mice. Acta Physiol Sin 2019; 71 (5): 689-697