神经生长因子与降钙素基因相关肽减轻局灶性脑缺血再灌注大鼠海马tau蛋白磷酸化

为探讨外源性神经生长因子(NGF)和降钙素基因相关肽(CGRP)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,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、Western Blotting和图像分析方法检测大鼠海马tau蛋白在Ser199/202位点磷酸化程度和总tau蛋白表达,以及NGF与CGRP对tau蛋白过度磷酸化的影响。结果显示:缺血再灌注组同侧海马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组及CGRP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);NGF与CGRP合用组海马tau蛋白磷酸化水平进一步降低,分别低于NGF组和CGRP组(P<0.05)。以上结果表明NGF及CGRP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,二者合用作用更强,降低缺血神经元tau蛋白磷酸化水平可能对缺血神经元起保护作用。

NGF and CGRP alleviate tau hyper-phosphorylation in rat hippocampus during focal cerebral ischemia-reperfusion

In order to explore the effect of exogenous nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) on tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia/reperfusion (I/R),focal cerebral ischemia/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 hippocampus during focal cerebral ischemia/reperfusion were detected by SABC immunohistochemical method and Western Blotting, and the positive products were analyzed by image analysis system. The present results showed that 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 those in the sham group (P<0.05).NGF and CGRP significantly reduced tau hyperphosphorylation at Ser199/202 site and the levels of total tau were significantly lower in NGF group and CGRP group than those in I/R group(P<0.05). Futhermore, the levels of tau phosphorylation in NGF and CGRP group were lower than those in NGF group and CGRP group, respectively(P<0.05). The above results indicate that NGF and CGRP can alleviate the level of tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia/reperfusion. Inhibiting tau hyperphosphorylation may be involved in the protective mechanism of NGF and CGRP to ischemic neuron. NGF and CGRP may cooperate with each other to promote the recovery of the ischemic neurons.