Effects of Valproic Acid and Molecular Hydrogen on Phenotypes of Microglia Treated with Hypoxia / 中国医科大学学报

ABSTRACT

Objective To investigate the effect of VPA and molecular hydrogen(H2)on phenotypes of microglia treated with hypoxia. Methods Mouse hypoxic BV2 microglia were treated with VPA or H2. The levels of phenotypic markers of supernatant and cells were detected by ELISA, flow cytometry and real?time PCR,respectively. Results Hypoxia significantly increased mRNA level of M1 marker(iNOS)and reduced mRNA levels of M2 markers(CD206 and TGF?β)in BV2(P<0.05). Besides,the ratio between the mRNA levels of M1 increased(P<0.05). VPA significantly reduced protein level(CD16/32)and mRNA production(iNOS)of M1 markers in hypoxia?treated BV2(P<0.05). The ratio be?tween the mRNA levels of M1 markers and M2 markers(CD16CD206,CD32CD206,iNOSCD206 and iNOSTGF?β)were also significantly decreased(P<0.05). H2 significantly reduced both protein levels(TNF?α,CD16/32 and iNOS)and mRNA production(iNOS)of M1 markers and increased secretion of M2 marker(IL?10)in hypoxia?treated BV2(P<0.05). The ratio between the mRNA levels of M1 markers and M2 markers(CD16CD206,iNOSCD206 and iNOSTGF?β)were also highly declined(P<0.05). Conclusion Hypoxia can induce microglial cells toward pro?inflammatory phenotype. Both VPA and H2 can inhibit hypoxia?induced inflammatory effect on microglia.