Protection and mechanism of oxygen glucose deprivation exposed astrocytes by nuclear factor-erythroid 2-related factor 2 signal pathway activation
GAO Yu-tian
WANG Ke-jian
WU Cheng-ji
HUANG Zuo-yi
Abstract：Objective To analyze the protective effect and mechanism of nuclear factor-erythroid 2-related factor 2(Nrf2)signal pathway agonist tertiary butylhydroquinone(tBHQ)on astrocytes under oxygen glucose deprivation(OGD).Methods Astrocytes were divided into 3 groups:the control group,the OGD group,and the tBHQ group.The cell proliferation activity after OGD and tBHQ intervention was assessed using the CCK-8 assay.Oxidative stress levels were evaluated by measuring superoxide dismutase(SOD)activity and malondialdehyde(MDA)content.The relative expression levels of pyroptosis-related genes(Caspase-1,NLRP3,IL-1β,IL-18)and antioxidant-related genes(HO-1,NQO1)were detected using real time fluorescent quantitative polymerase chain reaction(PCR).Results Significant differences were observed among different treatment groups in cell proliferation activity(F=8.676,P=0.003),SOD activity(F=5.818,P=0.013),MDA content(F=9.049,P=0.004),relative expression of pyroptosis-related genes Caspase-1(F=17.926,P=0.003),NLRP3(F=10.164,P=0.012),IL-1β(F=13.472,P=0.006),IL-18(F=8.292,P=0.019),and antioxidant-related genes HO-1(F=30.468,P=0.001),NQO1(F=29.621,P=0.001).Compared with the control group,the OGD group exhibited reduced cell proliferation activity(t=4.114,P=0.001)and SOD activity(t=2.149,P=0.029),increased MDA content(t=-2.852,P=0.015),upregulated expression of pyroptosis-related genes Caspase-1(t=-3.759,P=0.009),NLRP3(t=-4.119,P=0.006),IL-1β(t=-4.747,P=0.003)and IL-18(t=-3.122,P=0.021),and downregulated expression of antioxidant-related genes HO-1(t=3.816,P=0.009)and NQO1(t=5.303,P=0.002).Following tBHQ intervention,cell proliferation activity increased(t=2.621,P=0.019),SOD activity increased(t=3.292,P=0.005),MDA content decreased(t=-4.160,P=0.001),expression of Caspase-1(t=-5.916,P=0.001),NLRP3(t=-3.647,P=0.011),IL-1β(t=-4.193,P=0.006)and IL-18(t=-3.825,P=0.009)decreased,and expression of HO-1(t=7.805,P=0.000)and NQO1(t=7.483,P=0.000)increased.Conclusions OGD can suppress the expression of antioxidant-related genes HO-1 and NQO1,promote astrocytes pyroptosis and oxidative stress,and inhibit cell proliferation activity.Nrf2 signal pathway agonist tBHQ can enhance the expression of HO-1 and NQO1,reduce oxidative stress in OGD-exposed astrocytes,reverse pyroptosis,and exert protective effects on the cells.
Keywords：Ischemic strokeCell hypoxiaGlucoseAstrocytesNF-E2-related factor 2Cell proliferationPyroptosisCellscultured
Publication Date：2025-05-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 434-440 )