Ethyl Pyruvate Promotes Wound Healing in Elastase-Induced Lung Injury in Mice as Assessed by HyperpolarizedXe Magnetic Resonance Imaging.

Abstract

PURPOSE: Wound healing process in lung injury involves the 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 hyperpolarizedXe (HPXe) 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 HPXe MRI, revealing 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, HPXe MRI was performed to monitor the disease progression and treatment efficacy through changes in the metrics of gas exchange and fractional ventilation. RESULTS: HPXe 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 provide some insight into the role of the MAPK pathway in wound healing in elastase-induced lung injury, as assessed using the HPXe MRI protocol.