Mechanisms of Rat Gastrocnemius Muscular Atrophy Induced by Hindlimb Unloading

INTRODUCTION: Muscle atrophy is a critical health challenge during spaceflight. this study investigated the mechanism of muscle atrophy induced by 21-d hindlimb unloading (hlU) and metabolomic changes in rat gastrocnemius muscle (GM) and plasma. METHODS: the rat tail-suspended model was used to simulate microgravity. the effects of hlU on GM atrophy were assessed by measuring morphological changes, levels of oxidative stress factors and proinflammatory cytokines, and the expression of key proteins in the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase/ak strain transforming and nuclear factor-κB (NF-κB) signaling pathways. Metabolomic analysis of GM tissue and plasma was conducted to screen for differential metabolites associated with muscle atrophy under hlU conditions. RESULTS: hlU reduced the cross-sectional area of GM fibers and increased inflammatory factors interleukin-1β and tumor necrosis factor-α levels by 11.85% and 42.18%, respectively. levels of oxidative stress markers hydrogen peroxide and malondialdehyde in GM were increased by 17.95% and 112.19%, respectively. the hlU activated the NF-κB signaling pathway in GM and inhibited the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase/ak strain transforming pathway. Metabolomic analysis revealed nicotinamide and arachidonic acid levels were dramatically decreased and the kynurenic acid and glutaric acid levels were increased, which reduced peroxisome proliferator-activated receptor γ coactivator 1α and peroxisome proliferator-activated receptor γ protein expression, activating the NF-κB signaling pathway to promote proteolysis. DISCUSSION: the present study elucidated the potential mechanism of hlU-induced muscle atrophy at the metabolic level. these findings may supply potential biomarkers for astronaut health monitoring and be useful for clinical muscle atrophy treatment.