Ethyl Pyruvate Promotes Wound Healing in Elastase-Induced Lung Injury in Mice as Assessed by Hyperpolarized 129Xe Magnetic Resonance Imaging

Purpose Wound healing process in lung injury involves activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we investigated the role of the MAPK pathway in wound healing in a murine model of emphysema using hyperpolarized ¹²⁹ Xe (HP ¹²⁹ Xe) magnetic resonance imaging (MRI). Procedures Porcine pancreatic elastase was administered intratracheally to 25 mice to induce lung injury. Temporal changes in pulmonary gas exchange function were monitored using HP ¹²⁹ Xe MRI, which revealed a significant decline in function one day after elastase administration. Treatments with ethyl pyruvate (EP) and nicorandil (Nic), which upregulate and downregulate the MAPK pathway, respectively, were initiated in 12 and 7 of the 25 mice, respectively, and continued for 20 days. Over the 21-day period, HP ¹²⁹ Xe MRI was performed to monitor the disease progression and treatment efficacy through changes in the metrics of gas exchange and fractional ventilation. Results HP ¹²⁹ Xe MRI showed that EP significantly improved gas exchange function 14 days after elastase administration, whereas Nic did not show any improvement. Ventilatory function also improved in the EP group, but not in the Nic group, 14 days after elastase administration. Histological analysis showed that EP repaired tissue damage to a level similar to that observed in healthy mice, whereas Nic did not. Conclusions In the present study, we provided some insight into the role of the MAPK pathway in wound healing in elastase-induced lung injury, as assessed using the HP ¹²⁹ Xe MRI protocol.