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

TL;DR

This study shows that ethyl pyruvate improves lung wound healing in mice with lung injury, as measured by a special MRI technique.

Contribution

The study demonstrates that ethyl pyruvate promotes wound healing in lung injury by modulating the MAPK pathway, using hyperpolarized 129Xe MRI.

Findings

Ethyl pyruvate significantly improved gas exchange function in injured lungs.

Histological analysis confirmed tissue repair in the ethyl pyruvate-treated group.

Nicorandil did not show any improvement in lung function or tissue repair.

Abstract

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 hyperpolarized 129Xe (HP 129Xe) magnetic resonance imaging (MRI).

Porcine pancreatic elastase was administered intratracheally to 25 mice to induce lung injury. Temporal changes in pulmonary gas exchange function were monitored using HP 129Xe 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, HP 129Xe MRI was performed to monitor the disease progression and treatment efficacy through changes in the metrics of gas exchange and fractional ventilation.

HP 129Xe 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.

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 HP 129Xe MRI protocol.

The online version contains supplementary material available at 10.1007/s11307-025-02073-6.

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