TLR2 antagonist T2.5 attenuates cerebral ischemic injury by down-regulating of MMP-9 through MyD88 signaling pathway / 国际脑血管病杂志

ABSTRACT

Objective To investigate the mechanism of action of toll-like receptor 2 (TLR2),myeloid differentiation factor 88 (MyD88),and matrix metalloproteinase-9 (MMP-9) in cerebral ischemia-reperfusion injury in rats.Methods One hundred twenty-fiwe adult male SD rats were randomly divided into sham operation group,cerebral ischemia group and T2.5 (TLR2 antagonist) treatment group.A model of middle cerebral artery occlusion was induced by suture method.T2.5 (0.121 2 μg/g) was injected into jugular vein at the beginning of reperfusion in the T2.5 treatment group.Cerebral infarction volume,brain edema,bloodbrain barrier permeability and neurological deficit score were measured at 24 h after reperfusion.Western blotting was used to determine the expression levels of TLR2,MyD88 and MMP-9 at different time points in the ischemic cortex.Results Western blot analysis showed that compared with the sham operation group,the expression levels of TLR2 and MyD88 in the ischemic group increased significantly from 6 h after ischemia-reperfusion and lasted for 24 h (all P ＜ 0.05),while MMP-9 increased significantly at 24 h after ischemia-reperfusion (P ＜ 0.05).At 24 h after ischemia-reperfusion,the blood-brain barrier permeability,brain edema degree,cerebral infarction volume,and neurological deficit score in the ischemic group were significantly higher than those in the sham operation group (all P ＜0.05);at this time,the expression levels of TLR2,MyD88 and MMP-9 in the T2.5 treatment group were significantly lower than those in the ischemic group (all P＜ 0.05),and the blood-brain barrier permeability,brain edema degree,cerebral infarction volume,and neurological deficit score were significantly reduced (all P＜ 0.05).Conclusion TLR2,MyD88 and MMP-9 might be involved in cerebral ischemia-reperfusion injury.TLR2 antagonist T2.5 might inhibit the expression of MMP-9 through TLR2-MyD88 signaling pathway,thus alleviating cerebral ischemia-reperfusion injury.