The effect of lidocaine against sepsis-induced acute lung injury in a mouse model through the JAK2/STAT3 pathway

Abstract

Objective This study aimed to investigate the effects of lidocaine on sepsis-induced acute lung injury and its underlying mechanisms. Methods Thirty C57BL/6 mice were divided into three groups: SHAM, CLP, and LD. The sepsis-induced acute lung injury model was established using cecal ligation and puncture (CLP) surgery, while SHAM mice underwent a sham operation without ligation or puncture. Mice in the LD group were administered lidocaine (10 mg/kg) intravenously through the tail vein. The SHAM and CLP groups were treated with an equal volume of 0.9% sterile saline solution. All mice were sacrificed 24 hours after surgery, and lung tissue and blood samples were collected for subsequent analysis. The wet/dry weight ratio (W/D ratio) was measured to evaluate lung edema. Lung injury and apoptosis were assessed using HE staining and TUNEL assay. The concentrations of inflammatory cytokines IL-6, TNF-α, and HMGB1 were measured by ELISA. The expression of JAK2, STAT3, p-STAT3, Bcl-2, HMGB1, and Bax was analyzed by western blot. Results The W/D ratio in the CLP group was significantly higher than the SHAM group, indicating increased lung edema. Pathological examination revealed obvious lung injury, and apoptosis was evident in the CLP group. The expression of HMGB1, IL-6, and TNF-α in lung tissue increased by 24 hours after CLP surgery. Additionally, the levels of JAK2, STAT3, p-STAT3, HMGB1, and Bax were significantly increased, while Bcl-2 expression was reduced. However, lidocaine administration reversed these changes. Conclusion Intravenous lidocaine effectively alleviated acute lung injury in septic mice. The anti-inflammatory effects of lidocaine may be attributed to its suppression of the JAK2/STAT3 signaling pathway and its anti-apoptotic effects.