Electroacupuncture Alleviates Acute Kidney Injury in Septic Mice By Inhibiting the P2RX7/NLRP3 Signaling Pathway
Abstract
Objective
To investigate the protective effects and mechanisms of electroacupuncture on the P2X7 purinergic receptor/NLRP3 signaling pathway in sepsis-associated acute kidney injury (SA-AKI).
Methods
Healthy male C57BL/6J mice, 6-8 weeks old, were randomly assigned to the following groups: control, model, electroacupuncture, P2RX7 antagonist + model, and P2RX7 antagonist + model + electroacupuncture. The SA-AKI model was established by intraperitoneal injection of lipopolysaccharide (LPS). The P2RX7 antagonist A438079 was administered intraperitoneally 1 hour before LPS injection. Electroacupuncture (10 Hz, 0.5 mA, 30 min) was performed 1.5 hours after LPS injection. Mouse survival rates were assessed within 24 hours after modeling. Serum creatinine (Scr) levels were measured by blood biochemistry, IL-1β and IL-18 levels in serum and kidney tissues were measured with ELISA. Renal histopathological changes were observed by HE staining. Real-time fluorescent PCR and immunofluorescence assays were used to assess renal P2RX7 and NLRP3 expression levels.
Results
The 24-hour survival rate in the electroacupuncture group was 45%, a 15% improvement over the model group. Electroacupuncture treatment reduced renal histopathological damage, lowered Scr levels in SA-AKI (P < 0.05), and decreased serum inflammatory mediators IL-1β and IL-18 (both P < 0.0001). Electroacupuncture also reduced renal tissue expression levels of IL-1β (P < 0.0001), IL-18 (P < 0.001), P2RX7, and NLRP3 (both P < 0.05).
Conclusion
The mechanism by which electroacupuncture ameliorates SA-AKI may involve inhibition of the P2RX7/NLRP3 signaling pathway and attenuation of systemic inflammatory responses.
Keywords: Sepsis, Acute kidney injury, Electroacupuncture, P2RX7, NLRP3
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