Single-Cell RNA Sequencing Reveals the Therapeutic Effects of Electroacupuncture at BL23 on Hyperuricemia-Induced Nephritis.

Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA) level, which would trigger inflammatory processes contributing to kidney damage. Acupuncture stimulation of BL23, a therapeutic strategy in traditional Chinese medicine (TCM), has been reported to promote diuresis and suppress the immune system and seems to be efficacious in HUA. In this study, we aimed to investigate the effect of electroacupuncture (EA) at BL23 on HUA and HUA-induced kidney inflammation and dysfunction in mice. Mice received EA once daily after being given intragastric potassium oxonate (500 mg/kg) and adenine (100 mg/kg). EA administration not only decreased the levels of serum UA, creatinine, blood urea nitrogen, urinary UA, and protein, along with increased urinary CREA excretion, but also decreased the inflammatory cytokines productions (IL-1β, IL-6, and TNF-α) in serum. scRNA-seq of treated kidneys revealed that EA at BL23 suppressed the NLRP3 inflammasome complex, the IL-6/JAK/STAT3 signaling pathway, and the production of IL-6 and IL-1β in HUA mice. Western blot analyses verified that EA suppressed the HUA-induced NLRP3 inflammasome activation by promoting autophagy. In conclusion, the study demonstrated that EA at BL23 exhibited anti-HUA and nephroprotective effects by inhibiting both the NLRP3 inflammasome and the IL-6/JAK/STAT3 signaling pathway, reducing renal inflammation and supporting its therapeutic potential for HUA-associated kidney injury.