Objective To investigate the effect of cordyceps polysaccharide-functionalized selenium nanoparticles(Cs4-SeNPs)on lipopolysaccharide(LPS)-induced inflammatory response of BV2 microglial cells and its possible mechanism.Methods LPS-induced BV2 microglial cells were treated with different concentrations(0.01,0.10,1.00 μmol/L)of Cs4-SeNPs.MTT assay was used to measure the viability of BV2 microglial cells;Western blotting was used to measure the protein expression level of the selenoprotein glutathioneperoxidase 4(GPX4)in BV2 microglial cells,and quantitative real-time PCR was used to measure the mRNA expression levels of cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in BV2 microglial cells at diffe-rent time points(4,8,and 12 h).Results Cs4-SeNPs with a concentration of 0.01,0.10,and 1.00 μmol/L had no significant in-fluenceon the viability of BV2 cells.Compared with the control group,the LPS group had a significant reduction in the protein ex-pression level of GPX4(F=25.47,q=6.43,P<0.01),and compared with the LPS group,the 0.01,0.10,and 1.00 μmol/L Cs4-SeNPs treatment groups had a significant increase in the protein expression level of GPX4(q=5.72-14.07,P<0.01),with 1.00 μmol/L Cs4-SeNPs showingthe best effect(q=6.04-8.35,P<0.01).Compared with the control group,the LPS group had significant increases in the mRNA expression levels of COX-2 and iNOS(F=25.00,37.34;q=12.18,12.06;P<0.001).Pretreat-ment with 1.00 μmol/L Cs4-SeNPs for 12 h could significantly inhibit the mRNA expression of COX-2(q=6.10,P<0.05),and pretreatment for 8 and 12 h significantly inhibited the mRNA expression of iNOS(q=4.71,6.97;P<0.05).Conclusion Cs4-SeNPs has an inhibitory effect on LPS-induced inflammatory response in BV2 microglial cells,possibly by regulating the selenopro-tein GPX4.