Effect of mitochondrial oxidative stress on lead-exposed inflammatory activation of microglia
Objective:To investigate the role and mechanism of mitochondrial oxidative stress in lead(Pb)-in-duced microglial inflammation.Methods:BV2 microglia cells were divided into 4 groups and treated with 0 μmol/L(control group),1 μmol/L,5 μmol/L and 10 μmol/L lead acetate,respectively.The mRNA expression lev-els of interleukin(IL)-6,IL-8 and tumor necrosis factor(TNF-α)in microglia were detected by reverse transcrip-tion-quantitative PCR(RT-qPCR).The activation state of microglia and the expression of mitochondrial reactive oxygen species(mtROS)were observed by immunofluorescence,and the mitochondrial membrane potential was detected by JC-1.C57BL/6 mice were divided into control group,Pb exposure group(Pb group)(100 ppm),Mito-TEMPO treatment group(MitoTEMPO group)(5 mg/kg),MitoTEMPO combined with Pb treatment group(Mito-TEMPO+Pb group),and the levels of serum and cerebral cortex inflammatory factors IL-1β and TNF-α were de-termined by enzyme-linked immunosorbent assay(ELISA).The levels of NLRP3,Caspase-1 and IL-1β in the hippocampus of mice were determined by western blotting.Results:Pb could activate BV2 microglia cells.Com-pared with the control group,the levels of IL-6,IL-8 and TNF-αmRNA in the Pb group were increased in a dose-dependent manner,mtROS was increased,and mitochondrial membrane potential was decreased.MitoTEMPO could inhibit the activation of microglia in hippocampus of mice,decrease the levels of IL-1β and TNF-α in se-rum and cerebral cortex,and increase the levels of NLRP3,Caspase-1 and IL-1β proteins in hippocampus(all P<0.05).Conclusion:Pb induces mitochondrial oxidative stress,which can activate microglia.The mechanism may be related to NLRP3 inflammasome activation.
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