TSA抑制NF-κB/p50而减轻缺血性脑损伤-东南大学学报医学版

TSA抑制NF-κB/p50而减轻缺血性脑损伤

单位：南京大学医学院附属鼓楼医院,神经内科,江苏,南京,210008

分类号：R979.19, R-33

出版年·卷·期（页码）：2008·27·第四期（267-270）

摘要：

目的:研究曲古菌素A(TSA)对缺血再灌注性脑损伤小鼠的保护作用及其可能的分子学机制.方法:小鼠侧脑室立体定位注射TSA;插线法制备局灶性大脑中动脉缺血再灌注模型;神经功能评分进行行为学研究;TTC染色检测脑梗死面积;Western blot测定COX-2、iNOS、NF-κB/ p50的表达.结果:小鼠缺血再灌注损伤脑可出现明显的神经功能缺失,并出现较大面积的梗死灶,TSA能明显改善脑缺血再灌注损伤后的神经功能,减小脑梗死面积.缺血再灌注损伤脑组织COX-2、iNOS炎症蛋白和NF-κB亚单位p50蛋白表达增加,应用TSA后可显著抑制上述蛋白的表达.结论:TSA可通过抑制炎症反应对脑缺血再灌注损伤小鼠具有脑保护作用,此作用可能由NF-κB/p50途径介导.

Objective To investigate the protective effect of trichostatin A(TSA) on reversible middle cerebral artery occlusion(rMCAO) of mouse model and its possible mechanisms.Methods The present study employed a mouse rMCAO model to study effects of TSA,a HDAC inhibitor,on ischemia-induced brain infarction,neurological deficits,neuroinflammation(COX-2 and iNOS),and expression of NF-κB/p50 subunit protein.Results We found lateral ventricle injection of 1μg TSA 2 h before middle cerebral artery occlusion for 2 h of mouse markedly decreased the infarct size and improved neurological function,along with the reduction of protein levels of inflammatory mediators,such as COX-2 and iNOS.Furthermore,declined expression of NF-κB/p50 subunit protein was revealed by Western blot analysis,which might be involved in the regulation of inflammation.Conclusion TSA exerts protective effect on reversible middle cerebral artery occlusion by inhibiting inflammatory reaction,which is possibly related to NF-κB pathway.

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