左旋丁苯酞对脑缺血大鼠皮质β-淀粉样肽含量及Tau蛋白磷酸化的影响  

Effects of L-3-n-Butylphthalide on β-amyloid Peptide Contents and Phosphorylation of Tau Protein in Rats with Cerebral Ischemia

作　　者：罗超[1] 彭吉霞[1] 孙晓东[1] 王燕[1] 赵万红[1] 

机构地区：[1]湖北医药学院基础医学院,湖北十堰442000

出　　处：《湖北医药学院学报》2013年第3期191-194,共4页Journal of Hubei University of Medicine

基　　金：湖北省自然科学基金资助项目(2009CDZ023);湖北省十堰市科技局项目(ZD2011002)

摘　　要：目的:观察左旋丁苯酞(L-3-n-Butylphthalide,L-NBP)对脑缺血大鼠皮质β-淀粉样肽(Aβ1-42)水平以及Tau蛋白磷酸化的影响,探讨其可能的机制。方法:大鼠双侧颈总动脉结扎90 d,制备脑低灌注模型。实验分假手术组(Sham)、溶剂对照组(Vehicle)、药物治疗组(L-NBP 30 mg/kg和L-NBP 120 mg/kg组)。L-NBP治疗组连续给药45 d后,用Morris水迷宫检测大鼠的空间学习和记忆的能力后取大鼠脑皮质组织,用ELISA法检测Aβ1-42含量,用Westron blot方法检测Tau蛋白的磷酸化水平。结果:在水迷宫实验中,L-NBP组与溶剂对照组相比,增加了脑缺血大鼠在目标象限活动时间(P<0.05)。L-NBP组比溶剂对照组减少了大鼠皮质Aβ1-42含量(P<0.01),降低脑缺血大鼠皮质Tau蛋白Ser396的磷酸化水平(P<0.01)。结论:左旋丁苯酞可以改善脑缺血大鼠的学习记忆缺陷,减少了皮质Aβ1-42含量,从而降低Tau蛋白的磷酸化水平,并且具有一定的剂量依赖性。Objective To investigate the effects of L-NBP on β-amyloid peptide contents and Tau protein phosphorylation in cortex of rats with cerebral ischemia,and to explore its possible molecular mechanism.Methods Cerebral ischemic rat models were induced by ligating the bilateral common carotid arteries for 90 days.The rats were divided into sham group,solvent group and treatment groups(treating with a dose of 30 mg / kg and 120mg / kg L-NBP,respectively).The four groups were administered oil and L-NBP for 45 days,and then the spatial cognition was determined with place navigation test and spatial probe in Morris water maze.The β-amyloid peptide contents and Tau protein phosphorylation levels were detected with biochemical method.Results The results of Morris water maze showed that the time spent in platform-quadrant of L-NBP treatment groups was significantly longer than that of solvent group(P < 0.05).Compared with solvent group,the cortex Aβ1 42 contents and Tau protein phosphorylation levels were all decreased in L-NBP treatment groups(all P < 0.01).Conclusion L-NBP can improve the defect of cognition and decrease β-amyloid peptide contents thereby reducing phosphorylation of Tau protein levels in cortex of rats with cerebral ischemia in a dose-dependent manner.

关 键 词：左旋丁苯酞 Β-淀粉样肽 P-Tau蛋白 

分 类 号：R965[医药卫生—药理学]