Correlation of Inflammation Severity With Pulmonary Gas Exchange and MiRNA 126 in Trauma Patients

Trauma elicits a complex immune response aimed at eliminating perceived threats and restoring physiological homeostasis. This response is initiated through the activation of damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), which function as the initial "signal 0" in the inflammatory cascade. In trauma patients, the balance between pro-inflammatory and anti-inflammatory mediators may become dysregulated, resulting in heightened vulnerability to severe infections even from low-virulence microorganisms. Such dysregulation contributes to increased rates of systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and mortality. Elevated cytokine release and activation of macrophages and lymphocytes further intensify the inflammatory process and the severity of SIRS.

The lungs are particularly susceptible to inflammatory injury following trauma. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent major complications, characterized by increased vascular permeability and persistent pulmonary inflammation. Severe trauma, high thoracic injury scores, hypotension, metabolic acidosis, major fractures, and delays in treatment are factors known to contribute to ARDS development.

Under normal conditions, the lung maintains minimal alveolar fluid through a balance of vascular oncotic pressure, intact tight junctions, and effective lymphatic drainage. When this barrier is disrupted by trauma or inflammation, plasma proteins and fluid leak into the interstitium and alveolar spaces, leading to protein-rich pulmonary edema. Type I alveolar epithelial cells (AEC-I), which cover most of the alveolar surface and form a tight barrier essential for gas exchange, become damaged. Type II alveolar epithelial cells (AEC-II), responsible for surfactant production and epithelial repair, may lose function, resulting in alveolar collapse due to surfactant depletion. Consequently, lung compliance decreases, pulmonary arterial pressures rise, and ventilation-perfusion mismatch leads to hypoxemia.

The pathogenesis of ARDS involves multiple biological processes, including inflammation, apoptosis, and thrombosis. Early in the syndrome, pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, and IL-8 are released. Neutrophils accumulate within the pulmonary microvasculature and alveolar spaces, where they release reactive oxygen species, proteases, and other cytotoxic mediators, causing further epithelial and endothelial injury.

In recent years, microRNAs (miRNAs) have emerged as potential regulators in ARDS and other inflammatory lung injuries. miR-126, in particular, has been found to be elevated in animal models of lipopolysaccharide-induced lung injury and within exosomes derived from human endothelial progenitor cells. Experimental studies suggest that miR-126 supports the integrity of alveolar and endothelial barriers by enhancing tight-junction protein expression (such as claudins and occludin) and modulating signaling pathways involving PIK3R2, HMGB1, VEGFα105, Rac1, and AKT. These findings indicate that miR-126 may have a protective role in maintaining pulmonary barrier function, although no miRNA-targeted therapy is currently approved for ARDS.