Abstract: The microgial cells were used as a model to study the morphological changes, cell viability, and apoptosis induced by Pb²⁺. The metabolite levels in the microglial cells exposed to Pb²⁺ or solvent were measured using UPLC-QTOF mass spectrometry. The results show that a concentration of 10 μmol/L Pb²⁺ caused significant morphology changes, decreased cell viability, and increased the cell apoptosis of microglial cells. UPLC-QTOF mass spectrometry data showed that almost 973 potential metabolite levels were significantly changed with more than 1.5 folds (P < 0.05). Principal component analysis showed that Pb²⁺ exposure group and the normal control group had obviously different clustering trends.The pathway enrichment analysis of differential metabolites showed that Pb²⁺ significantly changed several key metabolism pathways involved in oxidation and reduction function, including glutamine/glutamate metabolism, ascorbate/aldarate metabolism, butanoate metabolism, and glutathione metabolism. These results provide an experimental basis and theoretical reference for the toxicity mechanism and alleviation drugs development of Pb²⁺.

Key words: Pb²⁺ toxicity, microglial cell, metabolomics, UPLC-QTOF mass spectrometry