Artificial Intelligence–Based Evaluation of ApoA-I’s Anti-Inflammatory and Anti-Fibrotic Roles in Experimental Pulmonary Injury

Abstract

Idiopathic pulmonary fibrosis (IPF) remains a progressive and fatal interstitial lung disease characterized by persistent epithelial injury, dysregulated tissue repair, and excessive collagen deposition. Emerging evidence suggests that apolipoprotein AI (ApoA-I), a key component of the pulmonary surfactant-associated lipid network, was exert protective effects within the injured lung microenvironment. The present study evaluated the anti-inflammatory and antifibrotic efficacy of ApoA-I in an experimental lung fibrosis model, integrating in vivo, histological, biochemical, and in vitro analyses. Lung fibrosis was induced by bleomycin, followed by therapeutic administration of ApoA-I, and outcomes were assessed through cytokine profiling, hydroxyproline quantification, oxidative stress assays, and fibroblast activation studies. ApoA-I treatment resulted in a notable 42–55% reduction in pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, compared with untreated fibrotic controls. Collagen accumulation and hydroxyproline content were significantly decreased by 47%, accompanied by an improvement in Ashcroft fibrosis scores from 5.8 to 2.4. Oxidative stress markers showed marked normalization, with malondialdehyde levels reduced by approximately 59% and superoxide dismutase and glutathione restored by 33% and 29%, respectively. ApoA-I also attenuated epithelial apoptosis, indicated by a 40% reduction in caspase-3 activity and a 52% increase in Bcl-2 expression. In vitro analysis demonstrated suppression of α-SMA expression by ~50%, confirming inhibition of fibroblast-to-myofibroblast transition. Collectively, these findings reveal that ApoA-I substantially mitigates inflammation, oxidative stress, epithelial injury, and extracellular matrix remodeling in fibrotic lungs. The outcomes support the therapeutic potential of ApoA-I as a multifunctional modulator capable of slowing or reversing fibrotic progression, providing a strong rationale for its further development as a candidate treatment for IPF.