AMPK/mTOR/ULK1通路激活的自噬参与AURKB介导的神经病理性疼痛中的小胶质细胞增生

Background: Neuropathic pain (NP) is linked to microglial activation and neuroinflammation; however, the regulatory mechanisms governing microglial autophagy in NP are not yet fully understood. This study investigates aurora kinase B (AURKB) as a regulator of autophagy and microgliosis through the AMPK/mTOR/ULK1 pathway. Methods: Rats underwent chronic constriction injury (CCI), and spinal microglia were exposed to lipopolysaccharide (LPS) to induce NP models both in vivo and in vitro. AURKB knockdown was achieved using viral vectors carrying AURKB-targeting shRNA. The mRNA expression levels of inflammatory cytokines (IL-1β, IL-6, CCL2) were examined using qPCR and ELISA. Immunofluorescence and Western blotting were employed to assess the levels of Iba1 and p-p38, autophagy markers (LC3, Beclin1, p62), and the activation status of the AMPK/mTOR/ULK1 pathway. Results: CCI and LPS significantly upregulated AURKB in spinal microglia, which was accompanied by dysregulation of autophagy, as evidenced by reduced levels of LC3 and Beclin1, along with elevated levels of p62. AURKB knockdown restored autophagy, resulting from notable increases in AMPK and ULK1 phosphorylation, coupled with a reduction in mTOR phosphorylation. Furthermore, AURKB knockdown reduced microglial activation, as indicated by lower levels of Iba1 and p-p38, and decreased the release of pro-inflammatory cytokines. Importantly, AMPK inhibition partially reversed these protective effects, confirming the role of the AMPK/mTOR/ULK1 pathway in regulating autophagy and microgliosis driven by AURKB. Conclusion: This study identifies AURKB as a novel regulator of autophagy and microgliosis in NP through the AMPK/mTOR/ULK1 pathway, highlighting its potential as a therapeutic target.