Neruoprotection is considered as one of important therapeutic approaches for ischemic stroke.Inflammation plays an important role in the pathogenesis of ischemic stroke,and the inhibition of inflammation in the ischem...Neruoprotection is considered as one of important therapeutic approaches for ischemic stroke.Inflammation plays an important role in the pathogenesis of ischemic stroke,and the inhibition of inflammation in the ischemic brain tissue may provide neuroprotective effect.In this study,we observed the influence of permanent middle cerebral artery occlussion（pMCAO） and transient MCAO（tMCAO） on NF-κB level and production of several inflammatory cytokines in injured hemisphere in mice,investigated the regulative effect of a new compound W026 B on these influences in the two MCAO models.In pMCAO model,10 μg/kg and 100 μg/kg of W026 B（i.v.） significantly reduced infarct volumes,100 μg/kg of W026 B significantly decreased neurologic deficit scores and brain water contents,and 10 μg/kg and 100 μg/kg of W026 B reduced Evans blue exudation from ischemic brain tissue.The level of NF-κB was elevated by 17.6 times in injured hemisphere,and the levels of TNF-α,IL-1β and IL-17 were elevated by 2.3 times,2.2 times and 3.8 times compared with the sham operation group,respectively,100 μg/kg of W026 B significantly reduced these inflammatory cytokines.In tMCAO model,the elevation of NF-κB,TNF-α,IL-1β and IL-17 was 2.3 times,1.4 times,1.5 times and 1.4 times compared with the sham operation group,respectively.Moreover,100 μg/kg of W026 B significantly decreased the levels of these inflammatory cytokines.In embolic MCAO mice model,W026 B alone significantly reduced infarct volumes,and combined application with tPA further reduced infarct volume.In conclusion,W026 B displayed significant protecive effect on three brain ischemia models.It could protect brain against injury induced by ischmia and ischemia-reperfusion through inhibiting the production of NF-κB,TNF-α,IL-1β and IL-17.These results suggest that W026 B has a value for further study.展开更多
基金National Natural Science Foundation of China(Grant No.81573333,81503060)
文摘Neruoprotection is considered as one of important therapeutic approaches for ischemic stroke.Inflammation plays an important role in the pathogenesis of ischemic stroke,and the inhibition of inflammation in the ischemic brain tissue may provide neuroprotective effect.In this study,we observed the influence of permanent middle cerebral artery occlussion（pMCAO） and transient MCAO（tMCAO） on NF-κB level and production of several inflammatory cytokines in injured hemisphere in mice,investigated the regulative effect of a new compound W026 B on these influences in the two MCAO models.In pMCAO model,10 μg/kg and 100 μg/kg of W026 B（i.v.） significantly reduced infarct volumes,100 μg/kg of W026 B significantly decreased neurologic deficit scores and brain water contents,and 10 μg/kg and 100 μg/kg of W026 B reduced Evans blue exudation from ischemic brain tissue.The level of NF-κB was elevated by 17.6 times in injured hemisphere,and the levels of TNF-α,IL-1β and IL-17 were elevated by 2.3 times,2.2 times and 3.8 times compared with the sham operation group,respectively,100 μg/kg of W026 B significantly reduced these inflammatory cytokines.In tMCAO model,the elevation of NF-κB,TNF-α,IL-1β and IL-17 was 2.3 times,1.4 times,1.5 times and 1.4 times compared with the sham operation group,respectively.Moreover,100 μg/kg of W026 B significantly decreased the levels of these inflammatory cytokines.In embolic MCAO mice model,W026 B alone significantly reduced infarct volumes,and combined application with tPA further reduced infarct volume.In conclusion,W026 B displayed significant protecive effect on three brain ischemia models.It could protect brain against injury induced by ischmia and ischemia-reperfusion through inhibiting the production of NF-κB,TNF-α,IL-1β and IL-17.These results suggest that W026 B has a value for further study.
