Beschreibung:
Aluminum compounds are widely distributed in nature and applied frequently in daily life, which is considered as an important environmental pathogenic factor of neurodegenerative diseases. Previous studies have suggested that aluminum can cause neuroinflammation, but the mechanism was unclear. Wistar rats were randomly divided into control group, 0.2% AlCl 3 , 0.4% AlCl 3 and 0.6% AlCl 3 groups according to body weight. The rat model of subchronic aluminum exposure was established by direct drinking water containing AlCl 3 for 12 w. Primary astrocytes were isolated and treated with aluminum chloride. YC-1 was adopted as an inhibitor of HIF-1α in vitro experiments. After aluminum exposure, astrocytes in rat cerebral cortex were gradually activated, colocalized with HIF-1α and inflammation factors released, α-KGDH in astrocytes was decreased and SDH was increased. There was an increase in colocalization of HIF-1α and PKM2. The levels of HIF-1α, PKM2, C-Myc, p-C-Myc (Ser62) and CLIC4 were significantly elevated. The mitochondrial membrane potential was reduced and then OX-mt DNA was released. The colocalization of OX-mt DNA and NLRP3 inflammasome was enhanced, and the contents of NLRP3, Caspase-1 and IL-1β were significantly increased. The intervention of YC-1 could rescue these impairments. Therefore, aluminum exposure could induce oxidative metabolism disorder to trigger HIF-1α-PKM2-C-Myc-CLIC4 pathway which activate NLRP3 inflammasome by mitochondrial dysfunction, and finally release more inflammatory factors