Peptide MOTS-c Protects Lungs from Heart-Lung Bypass Injury by Boosting Glycolysis

Patients undergoing cardiopulmonary bypass (CPB), a procedure where a machine temporarily takes over heart and lung function during surgery, frequently suffer from acute lung injury (ALI). This severe complication can lead to acute respiratory distress syndrome (ARDS), prolonged hospital stays, and increased mortality. Current therapeutic strategies are often insufficient, highlighting an urgent need for novel interventions. This study specifically addresses the knowledge gap regarding effective therapeutic strategies to mitigate CPB-induced ALI by targeting metabolic pathways.

The study revealed that MOTS-c treatment significantly ameliorated CPB-induced lung injury. Histopathological examination showed that MOTS-c reduced lung injury scores by 45% (p<0.01) compared to the control group, characterized by decreased alveolar septal thickening and neutrophil infiltration. Furthermore, MOTS-c significantly improved lung function, evidenced by a 30% increase in the partial pressure of oxygen (PaO2) and a 25% reduction in lung wet-to-dry weight ratio (an indicator of pulmonary edema). Inflammatory markers such as IL-6 and TNF-α in bronchoalveolar lavage fluid were decreased by 55% and 48% respectively (both p<0.001). Mechanistically, MOTS-c activated the AMPK-HIF-1α-PFKFB3 pathway, leading to a 2.5-fold increase in glycolysis in lung tissue. This metabolic shift appears crucial for cellular resilience against injury. > MOTS-c treatment significantly reduced lung injury scores by 45% and improved oxygenation by 30% while activating a key metabolic pathway, demonstrating potent protective effects against CPB-induced ALI.