染料木素磺酸钠对脑缺血再灌注损伤的保护作用及DREAM和PSD95的表达变化

The neuroprotection effects of GSS on cerebral Ischemia/reperfusion and expression of DREAM

目的研究染料木素磺酸钠(GSS)对脑缺血再灌注损伤的保护作用,并初步探讨转录抑制子DREAM及突触后致密区蛋白95(PSD95)表达的变化。方法以大鼠大脑中动脉栓塞制作局灶性脑缺血再灌注损伤模型,缺血后10min于舌下静脉给不同剂量的GSS。再灌注24h,行神经功能学评分。麻醉后,腹腔静脉取血并分离血清。取脑,一组前脑做TTC染色,测定脑梗死体积;另一组取损伤侧脑组织制成10%的脑组织匀浆,比色法测血清及脑组织匀浆LDH活性;另取半暗带区脑组织,Western blot方法检测脑组织DREAM蛋白的表达。结果模型组大鼠出现明显的脑梗死区及神经功能缺损,血清LDH活性升高(P<0.01),缺血侧脑组织LDH活性降低(P<0.05),皮层半暗带区脑组织DREAM蛋白表达降低(P<0.05),PSD95蛋白表达升高(P<0.001)。与模型组相比,1mg/kg及2mg/kg GSS治疗组脑梗死体积减小;神经功能评分降低(P<0.01,P<0.05),血清LDH活性降低(P<0.05),缺血侧脑组织LDH活性升高(P<0.05);2mg/kg GSS治疗组皮层半暗带区DREAM蛋白表达升高(P<0.01),PSD95蛋白表达降低(P<0.05)。结论 GSS对脑缺血再灌注损伤具有保护作用,其保护机制与GSS提高转录抑制子DREAM的表达,从而抑制NMDA受体介导的兴奋性毒性损伤有关。

Objective To explore the therapeutic effects of genistein sodium sulfonate（GSS） on cerebral ischemia/reperfusion injury and investigate the expression of downstream regulatory element antagonist modulator（DREAM）,a transcription repressor,and postsynaptic density protein 95（PSD95）.Methods A rat cerebral ischemia/reperfusion injury was made through embolization of the middle cerebral artery,and the injury was treated with GSS,using sublingual vein injection.The neurological score was valued using Longa＇s method.The cerebral tissue was stained using the TTC method,and the volume of infarction was investigated,the activities lactic dehydrogenase（LDH） in serum and brain tissue were measured colorimetric method.Moreover the expression of DREAM and PSD95 on half injury brain tissue was explored by Western blot assay.Result After treated with GSS,reductions in the neurological score,volume of infarction and activity of LDH in serum and an elevation in the activity of LDH in brain tissue were observed.At the same time,GSS group rats showed an increase in expression of DREAM on half injury brain tissue,while an decrease in PSD95.Conclusion GSS has certain therapeutic effects on cerebral ischemia/reperfusion injury because it enhances the expression of transcription repressor DREAM which down-regulated the excitatory toxicity of N-methyl-D-aspartate receptors.