Promotion of epileptic seizure through up-regulation of matrix metalloproteinase-9 by apoptosis signal-regulating kinase 1 in lithium-pilocarpine epilepsy model / 实用医学杂志

ABSTRACT

Objective To investigate the alteration of apoptosis signal-regulating kinase 1(ASK1)phos-phorylation and matrix metalloproteinase-9(MMP-9)expression after temporal lobe epilepsy(TLE),and to explore the role and mechanism of ASK1-MMP-9 signal in TLE. Methods The lithium-pilocarpine epilepsy model was established. The ASK1 phosphorylation and MMP-9 expression were detected by western blot and immunofluo-rescence histochemistry. Using ASK1 inhibitors,the regulating effects of ASK1 on MMP-9 expression were deter-mined. And the role of ASK1 and MMP-9 in epileptic seizure was explored by inhibition of ASK1 and MMP-9. Results The ASK1 phosphorylation and MMP-9 expression increased in hippocampus in epilepsy model ,exhibiting a temporal correlation with epileptic seizure. Inhibition of ASK1 activation reduced the expression of MMP-9. And the level of epileptic seizure was significantly reduced by the inhibition of ASK1 and MMP-9. Conclusions The hippocampal ASK1 phosphorylation and MMP-9 expression distinctly increase in TLE model ,and the MMP-9 expression is induced by ASK1 activation. The ASK1-MMP-9 signal plays an important role in TLE.