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).

MATERIALS AND

METHODS

The Sprague-Dawley rats were randomly divided into a control group, SAP-ALI group (SAP; rats were induced through retrograde injection of 5.0% sodium taurocholate into the pancreatic biliary ducts), SAP-ALI+Emodin group (Emodin; administered Emodin throug`h gavage to the rats following the modeling), and SAP-ALI+Fer-1 group (Fer-1; injected Fer-1). Then the pulmonary microcirculation and pathology were observed using a Moor instrument, HE staining, and electron microscopy (EM). The expression of related proteins in serum and lung tissue was determined using enzyme-linked immunosorbent assay (ELISA) and western blotting (WB). In vitro study, human umbilical vein endothelial cells (HUVECs) were exposed to lipopolysaccharide (LPS) and treated with DMSO, Emodin, and Fer-1. The expression of related mRNA and proteins in HUVECs was 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 suppresses the inflammatory cytokines, inhibits ferroptosis through upregulated GPX4 and SLC7A11 in lung tissue. In vitro, Emodin suppressed the ferroptosis response by increasing GSH/GSSG level, while decreasing MDA, ROS, and Fe² + levels in HUVECs. Furthermore, Emodin upregulates the expression of GPX4 and SLC7A11 , mitigates mitochondrial damage, and downregulates the expression of NCOA4 in HUVECs.

CONCLUSION

Emodin inhibits ferroptosis in HUVECs by attenuating NCOA4-mediated iron autophagy, thereby ameliorating pulmonary microcirculation disorders in SAP-ALI rats.