The Protection Of DMF On Condition Of The Oxidative Stress Induced By A?

Objective:1.To observe the effect of Dimethyl Fumarate on Nrf2,Nqo1 and HO-1 in oxidative stress induced by A?25-35 in the rat astrocytes and sh-sy5 y cells.2.To further study the mechanisms of Dimethyl Fumarate on Nrf2 activation in oxidative stress induced by A? by detecting Keap1,HDAC2 in the rat astrocytes and Keap1,CX3CL1 in sh-sy5 y cells.Methods: 1.The rat astrocytes and sh-sy5 y cells were separately co-cultured with A? 25-35 to induce oxidative stress and were all divided into A? group,A?+DMF group,A?+Si-nrf2 group,A?+Si-nrf2+DMF group.A? group was transfected with Nrf2-conRNA.A?+Si-nrf2 group was transfected with Nrf2-siRNA to knock down the expression of Nrf2.A?+DMF group was intervened with DMF(4?M)after transfected with Nrf2-conRNA.A?+Si-nrf2+DMF group was intervened with DMF(4?M)after Nrf2-siRNA transfection.The mRNA levels of Nrf2,Nqo1 and Ho-1 were detected by RT-PCR in each group.2.In the rat astrocytes and sh-sy5 y cells,the mRNA levels of Keap1 were detected by RT-PCR in A? group,A?+DMF group,A?+Si-nrf2 group,A?+Si-nrf2+DMF group.The protein level of HDAC2 was detected by Western blot in astrocytes and the level of CX3CL1 was detected in sh-sy5 y cells.Results: 1.Both in astrocytes and sh-sy5 y cells,the mRNA levels of Nrf2,Nqo1 and HO-1 in A?+Si-nrf2 group and A?+Si-nrf2+DMF group were significantly lower than A? group and A?+DMF group,respectively(P<0.05).The mRNA levels of Nrf2,Nqo1 and Ho-1 in A?+DMF group were significantly increased than A? group(P<0.05).2.Both in astrocytes and sh-sy5 y cells,the levels of Keap1 mRNA were significantly decreased in DMF group and Nrf2+DMF group compared with A? group and Nrf2 group,respectively(P<0.05).The levels of HDAC2 protein in astrocytes were significantly decreased in A?+DMF group and A?+Si-nrf2+DMF group compared with A? group and A?+ Si-nrf2 group,respectively(P<0.05).The levels of CX3CL1 protein in sh-sy5 y cells were significantly increased in A?+DMF group and A?+Si-nrf2+DMF group compared with A? group and A?+Si-nrf2 group,respectively(P<0.05).Conclusions: 1.Nrf2 can repress the oxidative stress induced by A?.DMF can up-regulate the level of Nrf2 to increase the expression of the antioxidiant response factors.2.DMF may up-regulate the level of Nrf2 to reduce oxidative stress induced by A? via decreasing HDAC2 expression in rat astrocytes.DMF may up-regulate the level of Nrf2 via increasing CX3CL1 and decreasing Keap1 expression together to reduce oxidative stress induced by A? in sh-sy5 y cells.