EA mitigates sepsis-induced liver injury by inhibiting the proinflammatory pathways IκBα/NF-κB and NLRP3-mediated pyroptosis.

Abstract

The primary focus of sepsis therapy is to alleviate organ dysfunction. Sepsis-associated liver injury (SALI) occurs in about 40 % of sepsis patients, yet targeted therapeutic strategies remain unavailable. Electroacupuncture (EA) has emerged as a potential adjunctive therapy for sepsis, owing to its capacity to modulate the neuroendocrine-immune network. This study aims to investigate whether EA can alleviate SALI and its potential mechanisms. A murine model of sepsis was established via cecal ligation and puncture (CLP). The Zusanli (ST36) and Neiguan (PC6) acupoints, known for their anti-inflammatory properties, were selected for EA intervention. Following CLP, mice received EA stimulation at ST36 and PC6 for 20 min daily over two consecutive days. The results showed that EA significantly improved survival and attenuated SALI. Transcriptomic profiling via mRNA-seq uncovered immune cell gene expression changes in response to EA. Bioinformatics analysis indicated that EA downregulated genes involved in proinflammatory responses and leukocyte migration, which were enriched in Toll-like receptors and NOD-like receptors signaling pathways. Further research confirmed that EA significantly reduced serum levels of the proinflammatory cytokines IL-6, TNF-α, and IL-1β in septic mice. Mechanistically, EA suppressed activation of the proinflammatory signaling pathway IκBα/NF-κB and concurrently attenuated pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD axis in immune cells.