Exosomal Circ_STAT1-AS Delivery Induced by Dexmedetomidine Modulates Microglial Polarization to Alleviate Diabetic Peripheral Neuropathy by Inhibiting JAK/STAT1 Pathway

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Backgruound Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus, characterized by neuroinflammation. Previous studies have shown that dorsal root ganglion (DRG) neurons can regulate microglial polarization. This study aims to investigate how exosomal circ_signal transducer and activator of transcription 1 (STAT1)-AS from dexmedetomidine (DEX)-treated DRG neurons affects microglial polarization in DPN. Methods Exosomes were isolated from DRG neurons and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. DPN rat model was established by high sugar and fat diet combined with streptozotocin injection. The sciatic nerve conduction velocity, mechanical withdrawal threshold, and thermal withdrawal latency of rats were measured. Hematoxylin & eosin staining and immunohistochemical staining of S100B were used to detect spinal cord tissue injury. Chromatin immunoprecipitation quantitative polymerase chain reaction detected the interaction between histone deacetylase 5 (HDAC5) and unc-13 homolog D (UNC13D) promoter, as well as the H3 acetylation at lysine 27 (H3K27) acetylation level in UNC13D promoter region. Results Exosomal circ_STAT1-AS secretion from DRG neurons was enhanced by DEX treatment. These exosomes inhibited microglial M1 polarization and facilitated its M2 polarization by suppressing S

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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