Objective To investigate the mechanism of Tongdu Zhiyu acupuncture in the treatment of post-stroke depression (PSD).

Methods  A randomized controlled trial was conducted. Sixty-two PSD patients from the Department of Brain Disease, the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine were enrolled and randomly assigned in a 1∶1 ratio to a control group (n = 31) or an experimental group (n = 31). All patients received basic treatment. The control group received ordinary acupuncture, while the experimental group received ordinary acupuncture combined with Tongdu Zhiyu acupuncture. The treatment period was 8 weeks. The primary outcome was the total score on the 24-item Hamilton Depression Scale (HAMD-24). Secondary outcomes included the National Institutes of Health Stroke Scale (NIHSS) score, Barthel index, peripheral blood mononuclear cell miR-223-3p expression, and serum levels of NLRP3, IL-1β, and IL-18.

Results  After treatment, all indicators in the experimental group improved significantly compared with baseline (all P < 0.05), and the improvements were significantly greater than those in the control group (all P < 0.05). The HAMD-24 score decreased from 17.87 ± 3.90 to 13.04 ± 3.55; the NIHSS score decreased from 23.29 ± 6.74 to 9.97 ± 5.81; the Barthel index increased from 32.29 ± 5.37 to 87.13 ± 6.82; miR-223-3p expression increased from 0.29 ± 0.07 to 0.98 ± 0.21; serum NLRP3 decreased from (65.84 ± 7.16) ng/L to (49.56 ± 4.89) ng/L; IL-1β decreased from (43.92 ± 7.25) pg/mL to (22.24 ± 4.76) pg/mL; and IL-18 decreased from (30.70 ± 4.13) pg/mL to (15.40 ± 3.09) pg/mL.

Conclusion  Tongdu Zhiyu acupuncture can improve neurological function in PSD patients. Its mechanism may involve upregulating miR-223-3p expression, inhibiting NLRP3 inflammasome activation, and reducing the release of pro-inflammatory cytokines such as IL-1β and IL-18, thereby alleviating depressive symptoms.