[Exploring the potential causes of sarcopenia in sepsis patients based on proteome sequencing].

OBJECTIVE: To explore the possible mechanisms underlying the occurrence and development of sarcopenia in clinical sepsis patients based on proteomic sequencing, and to identify potential targets for early intervention and treatment of sarcopenia in severe infectious states such as sepsis. METHODS: Muscle samples were obtained from two severe trauma patients with sepsis who underwent debridement treatment (sepsis group) hospitalized in the department of critical care medicine of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, and two non-sepsis patients who underwent open surgery (control group) in the department of orthopedics. Both were obtained through routine biopsy procedures. The morphology of muscle tissue was observed under a light microscope using hematoxylin-eosin (HE) staining; mitochondrial status in muscle tissue was observed under transmission electron microscopy. Further proteomic sequencing of muscle tissue was performed to compare and analyze proteins with significantly differentially expressed proteins. A threshold of fold change > 1.5 and P < 0.05 was set for significantly upregulated proteins, and fold change < -0.67 with P < 0.05 for significantly downregulated proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on the significantly differentially expressed proteins. RESULTS: : 2 291.77±807.77 vs. 4 570.29±1 687.53, P < 0.05). Electron microscopy revealed mitochondrial edema, vacuolization, and a decreased proportion of normal mitochondria [(16.8±10.0)% vs. (94.4±3.2)%, P < 0.05]. Compared with the control group, proteomic sequencing identified 171 significantly differentially expressed proteins in the sepsis group, including 122 significantly upregulated and 49 significantly downregulated proteins. GO analysis indicated that the top 10 enriched terms for upregulated significantly differentially expressed proteins were primarily related to response to stimulus and membrane-associated processes, including integral component of membrane, intrinsic component of membrane, detection of stimulus, detection of biotic stimulus, response to nutrient, endoplasmic reticulum membrane, endoplasmic reticulum subcompartment, detection of external biotic stimulus, nuclear outer membrane- endoplasmic reticulum membrane network and regulation of reactive oxygen species metabolic process. The top 10 enriched terms for downregulated significantly differentially expressed proteins were mainly associated with catalytic and metabolic processes, including 10-formyltetrahydrofolate catabolic process, folic acid-containing compound catabolic process, pteridine-containing compound catabolic process, 10-formyltetrahydrofolate metabolic process, oxidoreductase activity (acting on the CH-NH group of donors, NAD or NADP as receptors), oxidoreductase activity (acting on the CH-NH group of donors), folic acid-containing compound metabolic process, cellular modified amino acid catabolic process, dicarboxylic acid catabolic process and tetrahydrofolate catabolic process. These findings suggest that differentially expressed proteins in sepsis patients are significantly enriched in processes such as perception of biological stimuli and nutrient metabolism. KEGG pathway analysis revealed that the top 10 enriched pathways for differentially expressed proteins were mainly involved in detoxification and immune-related processes, including peroxisome, mineral absorption, nuclear factor-κB signaling pathway, influenza A, inflammatory bowel disease, nucleocytoplasmic transport, toxoplasmosis, herpes simplex virus 1 infection, ferroptosis and Leishmaniasis, indicating significant activation of peroxisomes and the nuclear factor-κB signaling pathway, and reduced mineral absorption activity in sepsis muscle tissue. CONCLUSIONS: Mitochondrial dysfunction-induced metabolic disorders may be a key factor in sarcopenia during sepsis. Targeting mitochondrial function to restore muscle metabolic homeostasis represents a potential therapeutic strategy for sarcopenia in severe conditions such as sepsis.