Emodin Alleviates Acute Pancreatitis‐Associated Acute Lung Injury by Inhibiting Serum Exosomal miRNA‐21‐3p‐Induced M1 Alveolar Macrophage Polarisation

Severe acute pancreatitis (SAP) is a common abdominal emergency in clinical practice. Approximately 20%–40% of patients with SAP will be associated with acute lung injury (SAP‐ALI), which is a major cause of death. Emodin (EMO) is a naturally occurring anthraquinone derivative with various pharmacological properties. EMO has a therapeutic effect on SAP‐ALI; however, the underlying mechanism remains unclear. Exosomes mediate intercellular communication in disease progression. Therefore, this study aimed to explore the role of serum exosomes in SAP‐ALI and the potential mechanisms by which EMO regulates the composition of exosomes for treatment. miR‐21‐3p was highly expressed in serum exosomes of the SAP group and exacerbated M1 polarisation of alveolar macrophages (AMs). EMO treatment reduced serum exosomal miR‐21‐3p and relatively attenuated M1 polarisation. Transfection with an miR‐21‐3p inhibitor attenuated LPS‐induced M1 polarisation of AMs in vitro; however, its effects were partially reversed when the downstream target gene PTEN was knocked down simultaneously. This study suggests that EMO reduced the enrichment of miR‐21‐3p in serum‐derived exosomes of rats with SAP, inhibiting the M1 polarisation of AMs caused by the transfer of miR‐21‐3p through the exosome pathway. This mechanism is related to miR‐21‐3p targeting of the PTEN/PI3K/AKT signalling pathway.