Electroacupuncture alleviates acute gastric mucosal injury in mice by shifting macrophage polarization via the cGAS-STING pathway.
Background
Acute gastric mucosal injury (AGMI) is a common gastrointestinal condition characterized by rapid damage to the stomach lining, often leading to pain, bleeding, and potentially ulcers. Current treatments primarily focus on acid suppression or mucosal protection, but these often lack comprehensive anti-inflammatory and regenerative effects. Macrophage polarization, specifically the balance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes, plays a critical role in tissue injury and repair. The cGAS-STING signaling pathway is a key innate immune sensor that, when activated, can drive inflammatory responses and M1 macrophage polarization, representing a potential therapeutic target for inflammatory conditions like AGMI.
Study Design
Researchers induced acute gastric mucosal injury (AGMI) in 30 C57BL/6 mice via intragastric absolute ethanol administration. Mice were divided into normal, model, and electroacupuncture groups. The electroacupuncture group received treatment at "Zhongwan" (CV12) and "Zusanli" (ST36) for 30 min, once daily for 5 consecutive days. Gastric mucosal injury was assessed using the Guth scoring method, HE and PAS staining. Macrophage polarization (M1/M2) was quantified by flow cytometry, while inflammatory cytokines (TNF-α, IL-6, IL-10, TGF-β) were measured by qPCR. Key protein expressions (ZO-1, Occludin, cGAS, STING, p-STING, p-IRF3, p-TBK1, iNOS, CD86, Arg-1, CD206) were analyzed via Western blot and immunofluorescence.
Results
In the model group, gastric mucosal injury index significantly increased (P<0.01), accompanied by epithelial necrosis and mucus layer destruction. This was associated with a significant increase in M1 macrophages and a decrease in M2 macrophages (P<0.01). Pro-inflammatory mRNA (TNF-α, IL-6) and protein (cGAS, STING, p-STING, p-IRF3, p-TBK1, iNOS, CD86) levels were elevated (P<0.01), while anti-inflammatory mRNA (IL-10, TGF-β) and protein (Arg-1, CD206) levels, along with tight junction proteins (ZO-1, Occludin), were reduced (P<0.01).
Key Findings
- Electroacupuncture decreased gastric mucosal injury index in mice (P<0.01).
- Electroacupuncture reversed macrophage polarization, decreasing M1 and increasing M2 macrophages (P<0.01).
- Electroacupuncture suppressed the
cGAS-STINGsignaling pathway activation (P<0.01). - Electroacupuncture reduced pro-inflammatory markers (
TNF-α,IL-6,iNOS,CD86) and restored tight junction proteins (ZO-1,Occludin) (P<0.01). - Electroacupuncture increased anti-inflammatory markers (
IL-10,TGF-β,Arg-1,CD206) (P<0.01).
Why It Matters
This study highlights electroacupuncture as a promising non-pharmacological intervention for acute gastric mucosal injury (AGMI), offering a novel mechanism beyond traditional treatments. By demonstrating its ability to rebalance macrophage polarization and suppress the cGAS-STING inflammatory pathway, it suggests a more holistic approach to mucosal healing and inflammation resolution. For individuals experiencing AGMI, electroacupuncture could represent a complementary or alternative therapy to reduce inflammation and promote tissue repair. While preclinical, these findings provide a strong rationale for further investigation into clinical applications, potentially informing future protocols for managing acute gastrointestinal inflammation. This mechanism-based understanding could also guide combination therapies, where electroacupuncture might enhance the efficacy of other mucosal protective agents.
electroacupuncture
acute gastric mucosal injury
agmi
macrophage polarization
cgas-sting
inflammation