This study assessed the metabolic effects of FLNPs, which were prepared using the Sendai virus envelope for gene delivery in a hindlimb ischemia model. Metabolomics was used to analyze gene and metabolite expression in the gastrocnemius muscle after treatment with Hepatocyte Growth Factor (HGF) and HGF-FLNPs.
Principal Component Analysis (PCA) revealed metabolic differences between the HGF and HGF-FLNPs groups, with FLNPs causing changes in lipid metabolism, likely due to the liposomes on the surface of the FLNPs. Further analysis using KEGG pathway annotation identified differential metabolites between the groups, with notable changes in lipid metabolism pathways. Hierarchical clustering and volcano plots visualized the differences in metabolite content, showing that 65 genes were up-regulated and 105 down-regulated in the HGF-FLNPs group.
The top 10 metabolites with the largest changes were displayed in a radar chart, including Anabasine, chondroitin D-glucuronate, and 17 alpha,21-dihydroxypregnenolone. KEGG pathway enrichment analysis highlighted significant changes in the regulation of metabolic pathways, particularly the down-regulation of the lipoic acid metabolic pathway and the up-regulation of the longevity-regulating pathway. The findings suggest that HGF-FLNPs may modulate cellular metabolism and promote longevity-related signaling, likely through the up-regulation of oleic acid.
3.4. HGF/CAT-FLNPs significantly improved gangrene, motor function and blood perfusion of ischemic hindlimbs