左旋丁苯酞对低灌注大鼠脑皮质Tau蛋白磷酸化的影响

目的通过观察左旋丁苯酞(1-NBP)对脑低灌注大鼠学习记忆的改善作用,并研究其皮质β-淀粉样肽(Aβ1-42)水平以及Tau蛋白磷酸化变化,以探讨1-NBP改善认识功能的作用机制。方法大鼠双侧颈总动脉结扎90d,制备脑低灌注模型。实验分假手术组,溶剂对照组,1-NBP 30、120mg/kg组。1-NBP治疗组连续给予45d后,用Morris水迷宫检测大鼠的空间学习和记忆能力,后取大鼠脑皮质组织,用酶联免疫吸附试验(ELISA)检测Aβ1-42含量,用蛋白印迹法检测Tau蛋白的磷酸化水平。结果在水迷宫空间探索实验中1-NBP明显增加脑低灌注大鼠在目标象限活动时间的百分比。1-NBP明显减少了大鼠皮质Aβ1-42含量,降低低灌注大鼠皮质Tau蛋白的磷酸化水平。结论 1-NBP改善了脑低灌注大鼠的学习记忆缺陷,可能是通过减少皮质Aβ1-42的水平,从而减轻Tau蛋白的磷酸化,最终保护了神经元免受损伤。

Effects of L-3-n-Butylphthalide on the P-Tau protein level in the cerebral cortex of cerebral hypoperfused rats

Objective To investigate the effects of 1-NBP onβ-amyloid peptide content and Tau protein phosphorylation changes in brain tissues of cerebral hypoperfused rats and to explore the possible molecular mechanism.Methods Cerebral ischemic rat models were induced by ligating the bilateral common carotid arteries for 90days.The rats were divided into four groups of sham,vehicle,1-NBP 30mg/kg and 120mg/kg.The four groups were administered oil and 1-NBP for 45days,and then the spatial cognition was determined with place navigation test and spatial probe in Morris water maze.Theβ-amyloid peptide content and Tau protein phosphorylation levels were detected with biochemical method.Results The time spent percentages in the platform-quadrant in 1-NBP groups was longer than vehicle groups(P<0.05).Meanwhile,ELISA results showed that the Aβ1-42expression level of 1-NBP 120mg/kg groups was less than vehicle groups(P<0.01)and Western blotting results showed that the Tau protein expression level of 1-NBP 120mg/kg groups was lower than vehicle groups(P< 0.01).Conclusion 1-NBP can improve the damage of cognition and decreaseβ-amyloid peptide content,thereby reducing phosphorylation of Tau protein levels in brain cortex of cerebral ischemic rats.