Glycyrrhizic Acid Attenuates Acute Lung Injury in Mice with Sepsis through PRDX6 Regulation of Cellular Iron Death
WANG Junmei1, REN Chunxiu2, JIN Lingling1, YU Guanghai1, BATU Wuliji2*
The aim of this paper was to investigate the protective effect and mechanism of GL (glycyrrhizic acid) on acute lung injury in sepsis. Fifty, 8-week-old, SPF-grade male BALB/C mice were randomly divided into 5 groups (10 mice in each group): SHAM-operated group (SHAM), model group (CLP), model+positive drug group (CLP+DEX) (dexamethasone), model+glycyrrhetinic acid low-dose (CLP+GLL) and model+glycyrrhetinic acid high-dose (CLP+GLH) groups. A mouse model of septic lung injury was established using cecum ligation and perforation. To investigate the role of ferroptosis in GL-mediated treatment of CLP, mice were intraperitoneally administered Lip-1 (liproxstatin-1, 0.8 mg/kg) 16 h prior to CLP surgery, followed by twice-daily intraperitoneal injections of 100 mg/kg glycyrrhizin for 7 days post-operation. The W/D (wet/dry weight) ratio of lung tissues was determined. HE staining was performed to check the pathological changes of lung tissues; cell counting of alveolar lavage fluid was performed in each group of mice; oxidative stress indexes in lung tissues were determined by kit and Fe2+ content was measured. qRT-PCR was performed to detect the expression of IL-6 and TNFɑ in lung tissues. Western blot was performed to detect the expression of PRDX6 and GPX4 expression in the lung tissues of mice in each group. Compared with the CLP group, GL effectively alleviated the rupture, deformation, fusion and inflammatory cell infiltration of alveolar structures in CLP mice, decreased the W/D ratio, reduced the total cell number, neutrophil number and macrophage number in BALF, decreased the expression of IL-6 and TNFɑ, lowered the expression of MDA and Fe2+, while GSH increased, the expression of GPX4 and PRDX6 proteins increased, and the expression of ACSL4 was down-regulated in a dose-dependent manner. Glycyrrhizic acid can effectively improve septic lung injury, reduce lung injury symptoms, and exert a protective anti-iron death effect, and increase PRDX6 expression.
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