Intratracheal Man-Rg3-Lipo Attenuates OLV-Induced Lung Injury in Juvenile Rats and Is Associated with Macrophage-Related NF-κB Suppression.

INTRODUCTION/OBJECTIVE: To determine whether intratracheally administered mannosemodified ginsenoside Rg3 liposomes (Man-Rg3-Lipo) mitigate One-Lung Ventilation (OLV)- induced lung injury in juvenile rats and to explore the associated pulmonary distribution, macrophage- associated inflammatory regulation, and NF-κB signaling changes. METHODS: Man-Rg3-Lipo was prepared by thin-film dispersion and characterized for morphology, particle size, Polydispersity Index (PDI), zeta potential, Encapsulation Efficiency (EE), Drug Loading (DL), and in vitro release. Ex vivo fluorescence imaging was performed after intratracheal administration to assess pulmonary distribution. An OLV model was established in male juvenile Sprague- Dawley rats with groups including MV, OLV, Man-Lipo, Rg3, and Man-Rg3-Lipo. Lung histopathology, tissue cytokines, NF-κB pathway activation, macrophage phenotype markers, and macrophage P65 nuclear localization were evaluated by hematoxylin-eosin staining, ELISA, Western blotting, and immunofluorescence. RESULTS: Man-Rg3-Lipo had a particle size of 142.3 ± 22.2 nm, a PDI of 0.268 ± 0.021, a zeta potential of -21.6 ± 7.7 mV, an EE of 92.46 ± 0.50%, and a DL of 8.46 ± 0.04%. After intratracheal delivery, fluorescence was concentrated in lung tissue; the paired mean difference between lung regions and other organs was 1.357 × 10^12 photons/s/cm²/sr (95% CI, 1.104 × 10^12 to 1.610 × 10^12; P = 0.0019). Compared with untreated OLV animals, Man-Rg3-Lipo reduced histopathological injury scores (4.10 ± 0.58 vs 9.90 ± 0.37; mean reduction, 5.80; 95% CI, 5.03 to 6.57; P < 0.0001), decreased IL-1β, IL-6, and TNF-α, restored IL-10, suppressed P65 and IκBα phosphorylation, decreased P65 nuclear localization in CD68-positive macrophages, and modulated CD86/CD163 macrophage phenotype markers. DISCUSSION: These findings indicate that local pulmonary delivery of Man-Rg3-Lipo may improve pulmonary exposure and attenuate OLV-associated inflammatory lung injury. The observed macrophage phenotype and NF-κB signaling changes support an associated mechanism, although receptormediated uptake and pathway dependence were not directly established. CONCLUSION: Intratracheal Man-Rg3-Lipo attenuated OLV-induced lung injury in juvenile rats. The protective effect was associated with pulmonary enrichment, reduced tissue-level inflammatory responses, inhibition of NF-κB activation, and macrophage-mediated regulation of inflammation. Further studies should evaluate dose-response relationships, repeated-dose regimens, pharmacokinetics, safety, and causal mechanisms.