摘要目的 研究曲古抑素A (trichostatin-A,TSA)是否可以作用于JAK激酶/信号转导和转录激活因子(Janus kinase/Signal transducer and activator of transcription,JAK/STAT)信号通路对大鼠的脑缺血-再灌注损伤的影响.方法 36只健康雄性SD大鼠随机(随机数字法)分成3组(n=12):假手术组、缺血-再灌注(ischemia/reperfusion,I/R)组、TSA处理组,采用大脑中动脉线栓法制作大鼠局灶性脑缺血-再灌注损伤模型,其中假手术组不进行线栓栓塞,TSA组栓塞前20min通过阴茎静脉注射TSA 0.05 mg/kg.3组制模成功后再灌注24 h,按照Longa 5分法进行大鼠神经功能缺损评定,脑切片TTC染色,ipp 6.0软件计算脑梗死体积百分比；每组随机取6只(n=6) Elisa检测JAK2蛋白的表达,其余6只(n=6)用于检测p-JAK2蛋白的表达.使用方差分析及非参数分析统计所得数据.结果 3组均有少量JAK2表达,组间差异无统计学意义(P=0.266)；与I/R组相比,TSA处理组神经学损伤评分降低(P =0.019),脑梗死体积缩小(P＜0.01),p-JAK2表达减少(P =0.009),组间差异有统计学意义.结论 TSA可一定程度地减轻脑缺血-再灌注损伤,发挥脑保护作用,这可能与TSA抑制p-JAK2介导的JAK/STAT信号通路有关.

abstractsObjective To investigate the protective effect of trichostatin-A (TSA) on cerebral ischemia/reperfusion injury via Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal pathway.Methods 36 male SD rats were randomly (random number) divided into 3 groups:shamoperated group,ischemia/reperfusion (I/R) group and TSA group.Rat model of middle cerebral artery occlusion/reperfusion (MCAO) was established using a modified filament method.No occlusion was applicated to the sham-operated group.TSA group was injected with TSA 0.05 mg/kg via penile vein,20 minutes before operation.Reperfusion was carried out 24 hours after modeling.Longa 5 score was used to assess the neurological function,and TTC staining was applied to calculate the percentage of cerebral infarction area,The expression of JAK2 and p-JAK2 proteins was detected by Elisa.Results The low expression of JAK2 was observed in each group,and there was no statistical difference between groups (P =0.266).Compared with I/R group,TSA group had lower score in cerebral ischemia-reperfusion injury assessment (P=0.019),smaller area of cerebral infarction (P ＜0.01),reduced expression of p-JAK2 (P =0.009),all of which were of significant difference.Condusions TSA can reduce the cerebral ischemia/reperfusion injury via JAK/STAT signal pathway by down regulating p-JAK2 expression.