NGF对局灶性脑缺血/再灌注大鼠海马tau蛋白磷酸化作用的影响

目的探讨外源性神经生长因子(NGF)对局灶性脑缺血/再灌注大鼠海马神经元tau蛋白过度磷酸化的影响。方法用线栓法制作局灶性脑缺血/再灌注模型,应用免疫组织化学SABC法、Westernblot和图像分析方法检测大鼠海马CA1区tau蛋白在Ser199/202位点磷酸化程度和总tau蛋白表达,以及NGF对tau蛋白过度磷酸化的影响。结果缺血/再灌注组海马CA1区tau蛋白在Ser199/202位点磷酸化水平和总tau蛋白明显升高(P<0·05);NGF组大鼠海马tau蛋白在Ser199/202位点磷酸化水平明显低于缺血/再灌注组,总tau也下降(P<0·05)。结论NGF明显减轻局灶性脑缺血/再灌注大鼠海马tau蛋白磷酸化程度,降低tau蛋白磷酸化水平可能对缺血神经元起保护作用。

Effect of NGF on tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia-reperfusion

Aim To explore the effect of exogenous nerve growth factor(NGF) on tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia/reperfusion(I/R).Methods Focal cerebral ischemi-a/reperfusion model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The level of tau hyperphosphorylation at Ser199/202 site and total tau in rat ispolateral hippocampal CA1 regions during focal cerebral ischemia/reperfusion were detected by SABC immunohistochemical method and Western blot,and the positive products were analyzed by image analysis system.Results The level of tau hyperphosphorylation at Ser199/202 site and total tau in rat hippocampal CA1 regions were significantly higher in I/R group than that in sham group(P<0.05).NGF significantly inhibited tau hyperphosphorylation at Ser199/202site and the level of total tau was lower in NGF group than that in I/R group(P<0.05).Conclusions NGF can reduce the level of tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia/reperfusion and inhibiting tau hyperphosphorylation may be involved in the protective mechanism of NGF to ischemic neurons.