不同剂量曲古抑素A后处理在脑缺血再灌注损伤中的脑保护作用

目的 观察不同剂量组蛋白去乙酰化酶抑制剂曲古抑素A(trichostatin-A,TSA)对大鼠短暂性大脑中动脉缺血再灌注损伤(Transient Middle cerebral artery occlusion,tMCAO)模型进行缺血后处理的脑保护作用.方法 健康雄性SD大鼠随机分为4组:I/R组、TSA组、溶剂对照组(DMSO)和假手术组(Sham).TSA组分为3个亚组,分别在大脑中动脉栓塞成功后立即尾静脉注射不同剂量的TSA:TSA1组——注射TSA 0.03mg/kg; TSA2组——注射TSA 0.1 mg/kg;TSA3组——注射TSA 0.3 mg/kg.分别于再灌注后6h和24 h进行神经功能缺陷评分,之后处死取材,行TTC染色测量脑梗死容积.结果 与sham组相比较,TSA组和I/R组均出现程度不同的神经生物学缺陷,神经功能缺陷评分在2～5分之间,sham组无神经功能缺陷.与I/R组相比较,TSA 0.3 mg/kg组无明显改善大鼠的神经功能缺损评分,与I/R组差异无显著性.TSA 0.03 mg/kg和0.1mg/kg组均可以降低神经功能缺陷评分,显著减少脑梗死容积,TSA 0.03 mg/kg和0.1 mg/kg组较I/R组分别减少脑梗死容积43.5％和42.8％.TSA 0.03 mg/kg组和0.1 mg/kg组相比较差异无显著性.结论 对tMCAO大鼠缺血后单次静脉注射0.03 mg/kg和0.1 mg/kg的去乙酰化酶抑制剂TSA可以减少脑梗死容积,改善神经生物学功能.而注射0.3 mg/kg的TSA却无显著的脑保护作用.

The protection of trichostatin-A against cerebral ischemia/reperfusion injury

【Objective】 To observe the protection of trichostatin-A(TSA) in different dose against transient middle cerebral artery occlusion(tMCAO) ischemia-reperfusion injury.【Methods】 Healthy male SD rats were randomly divided into 4 groups: I/R group,TSA group,vehicle(DMSO) group and sham operation group(Sham).TSA group was divided into three subgroups by the dosage: TSA1 group(0.03 mg/kg);TSA2 group(0.1 mg/kg);TSA3 group(0.3 mg/kg).The rats in TSA group were injected with tail vein of TSA immediately after preparation of MCAO model of ischemia.24 h after reperfusion,the neurological deficit score were evaluated,and then rats were sacrificed to measure infarct volume by TTC staining.【Results】 Compared with Sham group,there were different levels of neurobiological defects in TSA group and I/R group,the neurological deficit scores were between 2 and 5 points,and sham group had no neurological deficit.Compared with I/R group,neurological deficit score was no significant improved in TSA 0.3 mg/kg group.Neurological deficit score and infarct volume was significantly reduced in TSA 0.03 mg/kg and 0.1 mg/kg groups compared with I/R group.There were no significant differences between TSA 0.03 mg/kg and TSA 0.1 mg/kg groups.【Conclusions】 Single intravenous injection of 0.03 mg/kg and 0.1 mg/kg of deacetylase inhibitor TSA after tMCAO ischemia exerted significant brain protective effect,and the effect was not dose-dependent.But injection of 0.3 mg/kg TSA was not effective.