丹参对大鼠全脑缺血再灌注后海马CA1区AP-1 DNA结合活性的影响

The activation of AP-1 DNA binding activity in hippocampal CA1 subfield of rats following global brain ischemia-reperfusion and the effects of RSM

目的 探讨丹参对活化蛋白 1(AP 1)在缺血性脑损伤中的影响及其神经保护作用的机制。方法 采用颈动脉负压分流法制备大鼠全脑缺血再灌注模型 ,用EMSA法和组织化学法观察海马CA1区AP 1的DNA结合活性以及神经元形态改变。结果 (1)缺血再灌 3h ,丹参能不同程度的增加AP 1的结合活性 ,其中R6 0组较NS组明显增强 (P <0 0 5 ) ,R3 0组也有增强 ,活性由假手术组的 2 8倍增加为 3 0倍 ,但较NS组无显著性差异。同时RSM能不同程度的减轻再灌 72h和 7d的神经元损伤 ,CA1区存活细胞数目较NS组明显增加 (P <0 0 5 )。结论 丹参能明显提高缺血后海马CA1区AP 1的DNA结合活力 ,丹参的神经保护作用可能与其调节AP 1的DNA结合活力有关。

Objective To investigate the regulatory role of RSM on AP-1 DNA binding activity in hippocampal CA1 subfield of rats following global brain ischemia-reperfusion,and the molecular mechanism underlying protection of neurons against ischemic injuries in hippocampus.Methods The model of global brain ischemia-reperfusion was induced by means of carotid artery negative pressure shunt (CANPS).The EMSA and histochemical methods were used to evaluate the changes of the AP-1 DNA binding activity and cell structure in hippocampus.Results The administration of RSM 6.0 g/kg can significantly affect the AP-1 binding in the CA1 subfield from I/R group compared to that from NS group decapitated at 3 h after reperfusion(P<0.05);Similarly,with administration of RSM 3.0 g/kg,the AP-1 binding activity from I/R group was 3.0-fold compared to 2.8-fold from NS group, although no statistical significance was found between them.At 72 h and 7th day of reperfusion,RSM attenuated neuronal injury in the CA1 region and reduced necrosis cell counts to different extent(P<0.05). Conclusion The activity of AP-1 binding in hippocampal CA1 subfield can by potentiated by RSM.RSM may protect CA1 neurons against ischemia-reperfusion damage through molecular mechanisms associated with the modulation of AP-1 binding.