Abstract
Ulcerative colitis (UC), characterized by diffuse colonic inflammation and enteric nervous system (ENS) alterations, remains a therapeutic challenge. While the role of the parasympathetic nervous system in intestinal inflammation has been extensively documented, understanding of sympathetic nervous system (SNS) function in UC pathogenesis remains limited. Electroacupuncture (EA) at ST36 (Zusanli) is a widely used alternative therapy for UC, yet its regulatory effects on the ENS-particularly the SNS-and the underlying mechanisms remain unclear. Here, we established a 2.5% dextran sulfate sodium (DSS)-induced murine UC model and validated disease phenotypes via histological assessment. Using a non-anesthetic EA intervention protocol mimicking the clinical conditions, we found that EA at ST36 attenuated local inflammatory progression in DSS-induced UC mice and mitigated ENS degeneration. Critically, our results demonstrated that EA at ST36 specifically reversed SNS reduction (tyrosine hydroxylase-positive, TH+ neurons) in colonic tissue caused by intestinal inflammation. In conclusion, this study reveals that EA at ST36 restores colonic homeostasis through a sympathetic-dependent mechanism, providing novel insights and therapeutic strategies for the clinical management of UC.