Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

作者：Jiaquan Lin, He Tian, Xiaoguang Zhao, Sen Lin, Daoyong Li, Yuan‐ye Liu, Chang Xu, Xifan Mei · 发表于：CNS Neuroscience & Therapeutics · 年份：2020 · DOI：10.1111/cns.13460 · 被引用次数：66 · 研究领域：Spinal Cord Injury Research、Inflammasome and immune disorders、Autophagy in Disease and Therapy

AIM: Spinal cord injury (SCI) is a serious disabling injury worldwide, and the excessive inflammatory response it causes plays an important role in secondary injury. Regulating the inflammatory response can be a potential therapeutic strategy for improving the prognosis of SCI. Zinc has been demonstrated to have a neuroprotective effect in experimental spinal cord injury models. In this study, we aimed to explore the neuroprotective effect of zinc through the suppression of the NLRP3 inflammasome. METHOD: Allen's method was used to establish an SCI model in C57BL/6J mice. The Basso Mouse Scale (BMS), Nissl staining were employed to confirm the protective effect of zinc on neuronal survival and functional recovery in vivo. Western blotting (WB), immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of NLRP3 inflammasome and autophagy-related proteins. Transmission electron microscopy (TEM) was used to confirm the occurrence of zinc-induced autophagy. In vitro, lipopolysaccharide (LPS) and ATP polarized BV2 cells to a proinflammatory phenotype. 3-Methyladenine (3-MA) and bafilomycin A1 (BafA1) were chosen to explore the relationship between the NLRP3 inflammasome and autophagy. A coimmunoprecipitation assay was used to detect the ubiquitination of the NLRP3 protein. RESULTS: Our data showed that zinc significantly promoted motor function recovery after SCI. In vivo, zinc treatment inhibited the protein expression level ...