Lidocaine Attenuates miRNA Dysregulation and Kinase Signaling Activation in a Porcine Model of Lung Ischemia/Reperfusion Injury

Ischemia/reperfusion (I/R) injury is a major complication in lung transplantation. Recent evidence suggests that mitogen-activated protein kinases (MAPKs) such as p-38 mitogen-activated protein kinase (p-38 MAPK) and extracellular signal-regulated kinase (ERK), along with functionally related kinases like phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), contribute to I/R pathophysiology by mediating inflammatory and stress-response signaling. MicroRNAs (miRNAs) also play a regulatory role in these processes. Lidocaine has demonstrated anti-inflammatory activity in several tissues; however, its ability to modulate miRNA expression and kinase activation in the lung is not yet fully understood. This study investigated the involvement of these signaling molecules in lung I/R injury and evaluated the modulatory effect of intravenous lidocaine in a porcine lung auto-transplantation model. Eighteen large white pigs were assigned to sham-operated (<i>n</i> = 6), control (lung auto-transplantation, <i>n</i> = 6), or lidocaine-treated (<i>n</i> = 6) groups. Lidocaine was administered as a 1.5 mg/kg bolus followed by a continuous infusion (1.5 mg·kg^-1·h^-1). Lung biopsies were collected before ischemia, before reperfusion, and at 30- and 60-min post-reperfusion to assess total and phosphorylated levels of p-38 MAPK, ERK, PI3K, and AKT (Thr308, Ser473), along with miR-126, miR-142-5p, miR-152, and miR-155 expression. I/R increased p-38 MAPK and AKT, and enhanced phosphorylation of all four kinases. miRNA levels were also upregulated. Lidocaine partially or completely attenuated these changes. These findings support a role for these molecular pathways in lung I/R injury and suggest that lidocaine may offer protective effects through their modulation.