Emodin Alleviates Microcirculation Disorders in Acute Lung Injury Associated with Severe Acute Pancreatitis by Inhibiting Ferroptosis of Vascular Endothelial Cells

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Emodin on pulmonary microcirculation disorders in acute lung injury associated with severe acute pancreatitis (SAP-ALI). METHODS: The Sprague-Dawley rats were randomly divided into control group, SAP-ALI group(SAP)(rats was induced via retrograde injection of 5.0% sodium taurocholate into the pancreatic biliary ducts), SAP-ALI+Emodin group(Emodin)(administered Emodin via gavage to the rats following the modeling), SAP-ALI+Fer-1 group(Fer-1)(injected Fer-1). Then the pulmonary microcirculation and pathology was observed using Moor instrument, HE staining and electron microscopy(EM). The expression of related proteins in serum and the lung tissue was determined using enzyme-linked immunosorbent assay(ELISA),Western blotting (WB). In vitro study, Human Umbilical Vein Endothelial Cells (HUVECs)were exposed to lipopolysaccharide (LPS) and treated with DMSO,Emodin,Fer-1. The expression of related mRNA and proteins in HUVECs were detected using real-time polymerase chain reaction (RT-PCR), WB,EM and fluorescence microscopy. RESULTS: Emodin ameliorate pulmonary microcirculation disorders in SAP-ALI rats and suppressed the inflammatory cytokines, inhibits ferroptosis through upregulated GPX4 and SLC7A11 in lung tissue. In vitro, Emodin suppressed the ferroptosis response by increased GSH/GSSG level, while decreased MDA, ROS, and Fe²+ levels in HUVECs. Furthermore, Emodin upregulate the expression of GPX4 and SLC7A11, mitigate mitochondrial damage, and downregulate the expression of NCOA4 in HUVECs. CONCLUSION: Emodin inhibit ferroptosis in HUVECs by attenuating NCOA4-mediated iron autophagy, thereby ameliorating pulmonary microcirculation disorders in SAP-ALI rats.