左旋千金藤啶碱抑制Tau蛋白过度磷酸化改善帕金森病认知症状的相关机制研究

Study on the Related Mechanism of l-stepholidine Inhibited Phosphorylation of Tau Protein to Improve Cognitive Symptoms in Parkinson Disease

关键词:  左旋千金藤啶碱  帕金森病  认知症状  Tau蛋白

Key words:  l-stepholidine  Parkinson disease  cognitive symptoms  Tau protein

摘要:

目的 探讨左旋千金藤啶碱改善帕金森病（Parkinson disease，PD）认知症状的功能与Tau蛋白磷酸化程度之间的关系。方法 将150只大鼠随机分为空白对照组、1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-Methyl-4-phenyl-1，2，3，6-tetrahydropyridine hydrochloride，MPTP）组及给药组，每组50只。用MPTP建立PD大鼠模型。先测定各组大鼠的体质量，然后通过水迷宫对大鼠的逃避潜伏期、游泳时间百分比以及海马锥体细胞顶树突分支数目和直径进行比较。对大鼠海马神经元进行采集，通过酶联免疫吸附测定（enzyme linked immunosorbent assay，ELISA）法对Tau蛋白的磷酸化程度进行计算。最后对大鼠的海马组织进行采集，利用流式细胞仪对大鼠海马神经元的凋亡率进行测定。结果 与对照组相比，MPTP组的体质量、游泳时间百分比、锥体细胞顶树突分支数目、海马P-Tau蛋白表达明显降低（P<0.05），逃避潜伏期明显延长（P<0.05），脑外伤海马神经元细胞的凋亡率明显升高（P<0.05）；与MPTP组相比，给药组体质量、游泳时间百分比、锥体细胞顶树突分支数目、海马P-Tau蛋白表达明显升高（P<0.05），逃避潜伏期、脑外伤海马神经元细胞的凋亡率明显降低（P<0.05）。结论 左旋千金藤啶碱对PD模型大鼠具有保护作用，抑制Tau蛋白的过度磷酸化是左旋千金藤啶碱保护神经元的可能机制。

Abstract:

OBJECTIVE To investigate the relationship between the improvement of cognitive symptoms correlation function and the degree of Tau protein phosphorylation in Parkinson disease (PD) treated by l-stepholidine.METHODS One hundred and fifty rats were randomly divided into 3 groups, including blank control, MPTP group, drug group, 50 rats in each group. The PD rats model were established with MPTP. The body weight of rats were determined, than the latency time and the percentage of the swimming time through the Water Maze, the number and diameter of the apical dendritic branches in the hippocampal pyramidal cells were compared. The hippocampal neurons of rats were collected and the phosphorylation of P-Tau protein was calculated by enzyme linked immune sorbent assay (ELISA) method. Finally, the hippocampal tissues of rats were collected, and the apoptosis rate of hippocampal neurons was measured by flow cytometry.RESULTS Compared with the control group, the body mass, percentage of swimming time, the number the apical dendritic branches and the expression of P-Tau protein in MPTP group were significantly decreased in drug group (P<0.05), while the latency time was significantly prolonged(P<0.05), and the apoptosis rate of hippocampal neurons was increased significantly(P<0.05). Compared with MPTP group, the body mass, percentage of swimming time, the number of the apical dendritic branches in the hippocampal pyramidal cells and the expression of P-Tau protein in hippocampus were increased significantly in drug group (P<0.05), while the the latency time and cell apoptosis rate decreased significantly (P<0.05).CONCLUSION l-stepholidine has protective effects on rats model of PD, hyperphosphorylation of Tau protein is the possible mechanism of inhibition of l-stepholidine protects dopaminergic neurons.