Improving Lung Injury in Sepsis-Related Systemic Inflammatory Response Syndrome Through Regulation of the TLR4/NF-κB Pathway and Macrophage Polarization by Ganoderic Acid A

Abstract

This study aimed to investigate the effects and mechanisms of Ganoderic acid A (GAA) on lung injury associated with systemic inflammatory response syndrome (SIRS). Forty Sprague Dawley rats were divided into four groups: Control group, GAA group (GAA, 40 mg/kg), lipopolysaccharide (LPS) group (LPS, 10 mg/kg), and LPS + GAA group. Lung tissue, bronchoalveolar lavage fluid (BALF), and blood samples were analyzed for cell counts, protein levels, and histology, inflammatory cytokines, oxidative stress markers, and macrophage polarization. Western blot was used to assess the TLR4/NF-κB pathway. GAA treatment significantly attenuated LPS-induced lung injury, as shown by reduced lung tissue water content and BALF protein levels. Histological analysis confirmed less severe lung injury in GAA-treated rats. GAA decreased inflammatory cell numbers in BALF, lowered inflammatory cytokine levels in serum and BALF, and reduced oxidative stress levels in lung tissue. Flow cytometry indicated that GAA promoted M2 macrophage polarization, and Western blot analysis revealed inhibition of TLR4/NF-κB pathway activation. GAA ameliorates lung injury induced by sepsis-related SIRS in rats through anti-inflammatory, anti-oxidative, and immunomodulatory effects, supporting its potential therapeutic value in sepsis treatment.