左旋丁苯酞对低灌注大鼠脑皮质Tau蛋白磷酸化的影响

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

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。

Objective To investigate the effects of 1-NBP on β-amyloid peptide content and Tau protein phosphorylation changes in brain tissues of cerebral hypoperfused rats and to explore the possible molecular mech- anism. Methods Cerebral ischemie rat models were induced by ligating the bilateral common carotid arteries for 90 days. The rats were divided into four groups of sham, vehicle, 1-NBP 30 mg/kg and 120 mg/kg. The four groups were administered oil and 1-NBP for 45 days, and then the spatial cognition was determined with place nav- igation test and spatial probe in Morris water maze. The ^-amyloid peptide content and Tau protein phosphoryla- tion 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 Aβ1-42 ex- pression level of 1-NBP 120 mg/kg groups was less than vehicle groups （P〈O. 01） and Western blotting results showed that the Tau protein expression level of 1-NBP 120 mg/kg groups was lower than vehicle groups （P〈 0.01）. Conclusion 1-NBP can improve the damage of cognition and decrease β-amyloid peptide content, thereby reducing phosphorylation of Tau protein levels in brain cortex of cerebral ischemic rats.