脑低灌注触发脑内tau过度磷酸化和胆碱能神经损害

目的 探讨脑低灌注对脑内tau蛋白的过度磷酸化和胆碱能指标变化的影响.方法 40只SD大鼠随机分为低灌注组和假手术组,永久性阻断双侧颈总动脉制作脑低灌注模型;应用Y迷宫检测大鼠学习记忆能力,用免疫组化法检测大脑皮质和海马组织色氨酸404位点tau蛋白过度磷酸化(Pser404-Tau)和胆碱乙酰转移酶(ChAT)的表达,用考马斯亮蓝法检测海马组织乙酰胆碱酯酶(AChE)活性.结果 脑低灌注术后14 d和21 d,大鼠学习记忆能力明显减退,与假手术组相比差异有统计学意义(P＜0.01);大脑皮质和海马组织Pser404-Tau阳性细胞数较假手术组明显增加(P＜0.01);大脑皮质和海马组织ChAT阳性细胞计数较假手术组明显减少(P＜0.01);海马组织AChE活性较假手术组明显降低(P＜0.01).结论 脑低灌注后出现认知功能障碍,可能与脑缺血导致脑内tau蛋白过度磷酸化、损害胆碱能神经功能有关.

Cerebral hypoperfusion initiated tau hyperphosphorylation and impaired cholinergic nervous system in rat brain

Objective To explore the effects of cerebral hypoperfusion on the tau hyperphosphorylation and impaired cholinergic nervous system in rat brain.Methods Forty young adult rats were randomly divided into hypoperfusion group and sham operated group.Bilateral common carotid arteries were permanently occluded to mimic the cerebral hypoperfusion.The spatial learning and memory ability of rats was tested by Y-maze before operation and 14 days and 21 days after operation respectively.The protein expression of Pser404-Tau and choline acetyltransferase(ChAT)in cortex and hippocampus was detected with immunohistochemistry.The hippocampal acetylcholinesterase(AChE)activity was measured by Coomassie brilliant blue method.Results Rats showed spatial memory deficits at 14 days and 21 days after hypoperfusion,the difference was significant between sham operated group and hypoperfusion group(P<0.01).The expression of Pser404-Tau in cortex and hippocampus was higher in hypoperfusion group than in sham operated group(P<0.01),whereas the expression of ChAT was much lower in hypoperfusion group than in sham operated group(P<0.01).The hippocampal AChE activity in hypoperfusion group was less than that in sham operated group(P<0.01).Conclusion Cerebral hypoperfusion induced a marked memory impairment.It might be related with hyperphosphorylation of tau protein and then injuries of cholinergic nervous system following cerebral ischemia.