阿魏酸钠对局灶性脑缺血突触后致密物质-95活化的影响

Effect of sodium ferulate on activation of postsynaptic density95 after transient focal cerebral ischemia

目的 :观察阿魏酸钠 (SF)对局灶性脑缺血损伤的保护作用及其对突触后致密物质 95 (PSD 95 )活化的影响。方法 :雄性 SD大鼠 4 6只 ,随机分成对照组和 SF组 (每组各 2 3只 ) ,分别于缺血时腹腔注射生理盐水 4 m l和 SF1 0 0 m g/ kg(用生理盐水 4 m l溶解 )。采用线栓法制备大脑中动脉阻闭 (MCAO)模型 ,1 6只大鼠(每组各 8只 )在脑缺血再灌注后 2 4 h神经行为学评分完成后被处死 ,取大脑行氯化三苯四唑 (TTC)染色以测量脑梗死容积 ;其他大鼠在脑缺血再灌注后的 30 m in、2 h、6 h、2 4 h和 72 h(各组每个时间点 3只 )分别被处死 ,取缺血侧和对侧皮质以及缺血侧纹状体行 Western blot分析。结果 :术后动物均存活。再灌注 2 4 h神经功能缺损评分对照组明显高于 SF组 ,SF组动物梗死容积〔(6 1 .5± 2 8.7) mm3〕明显小于对照组〔(1 6 8.1±4 2 .2 ) m m3,P<0 .0 1〕。 Western blot分析法表明 ,对照组再灌注 30 m in后 PSD 95在缺血皮质和纹状体活化显著增多并出现高峰 ,持续 72 h;在 SF治疗组 ,再灌注后 30 min PSD 95活化开始增多 ,高峰出现在 2 h,6 h后开始下降 ,而且 PSD 95活化在各时间点较对照组少 ,持续时间短。在对侧皮质未发现 PSD 95的活化。结论 :SF对局灶性脑缺血损伤有神经保护作用 。

Objective: To study the neuroprotection of sodium ferulate(SF) and effect of SF on activation of postsynaptic density95(PSD95) after transient cerebral artery occlusion in rats. Methods: Fortysix male SpragueDawley rats were randomly divided into two groups ( n =23 in each group): control group and SF group. They received intraperitoneal normal saline 4 ml and SF 100 mg/kg which was dissolved in 4 ml normal saline respectively when the rats were ischemic. Middle cerebral artery occlusion(MCAO) model was used. At 24 hours after reperfusion, 16 animals( n =8 in each group) were assessed by neurological scale, and brain tissue was taken to assess the infarct volume with 2, 3, 5triphenyltetrazolium chloride(TTC) staining. The other rats( n =3 at different timepoint in each group) were decapitated at 30 minutes, 2 hours, 6 hours, 24 hours and 72 hours after reperfusion. Immediately the activation of PSD95 was measured using Western blot analysis system in ischemia and contralateral cortex and striatum of rat brain. Results: All the rats survived after operation. The neurologic deficit score of rats in SF group decreased significantly compared with control group( P <0.01). The infarct volume of control group 〔(168 1±42 2) mm 3〕 was significant greater than those of SF group〔(61 5±28 7) mm 3, P <0 01〕 at 24 hours after reperfusion. The ischemic cortex and striatum in control group showed a markedly increased level of PSD95 activation and peaked at 30 minutes after reperfusion. Activation of PSD95 was moderately increased 30 minutes after reperfusion, and peaked at 2 hours, followed by a moderate decline at 6 hours in SF group. Moreover, activation of PSD95 at each time point in SF group was less than that in control group, and activation of PSD95 persisted a shorter course in SF group than in control group. No upregulation of PSD95 protein could be detected in the contralateral cortex. Conclusion: SF could induce neuroprotective effects in transient focal cerebral ischemic injury, weaken PSD95 activation in ischemic area.