Damage control orthopedic treatment upregulates anti-inflammatory miR-21/23a/27a and miR-30b expression in lung tissue of polytraumatized pigs

MicroRNAs, important post-transcriptional gene regulators, may play a regulatory role in the activation and progression of regenerative responses after polytrauma. The aim of this study was to validate the expression of a selection of miRNAs with known involvement in pulmonary pathologies relevant for the polytrauma setting, in a porcine polytrauma model comparing two surgical treatment methods, as well as one treatment group that additionally to standard surgical care received C5/CD14 inhibition (drug-based treatment).

Methods

The porcine polytrauma model consisted of blunt chest trauma, bilateral femur fractures, liver laceration, and hemorrhagic shock. Four groups were defined: sham, early total care (ETC: n=8), damage control orthopedics (DCO: n=8), ETC with C5/CD14 inhibition medication (n=4). Animals were monitored and treated in an ICU-setting including volume-controlled, mechanical ventilation for 72 hours.

After sacrifice, lung samples were taken from the left lobe. MiRNAs were isolated, transcribed, and analyzed by qPCR. Furthermore, Periodic Acid Schiff (PAS) staining and in situ hybridization were performed.

Results MiRNAs associated with lung function, inflammation, and fibrosis were analyzed. Compared to ETC, DCO resulted in less inflammatory and fibrotic miRNA expression, consistent with histological findings showing more preserved alveoli, less septal thickening, and fewer inflammatory cell infiltrations. The addition of anti-C5/CD14 to ETC further reduced the expression of inflammatory and fibrotic microRNAs compared to both DCO and ETC and showed a significant reduction in histopathological changes in the lung tissue.

Conclusions This study showed that C5/CD14 inhibition therapy effectively reduced histopathological changes in the lung tissue combined with less inflammatory and fibrotic miRNA expression, compared to both the DCO and ETC groups. Further research should focus on the long-term effects of this dual therapy on tissue regeneration in the polytrauma patient.