当归对慢性脑低灌注大鼠阿尔茨海默病样变与认知功能的影响

Effect of Radix Angelica Sinensis on Alzheimer's disease-like lesions and cognitive function in rats with chronic cerebral hypoperfusion

目的观察当归对慢性脑低灌注大鼠阿尔茨海默病样变及认知功能的影响。方法选择SD大鼠44只,随机分为假手术组、双侧颈总动脉结扎模型(2VO)组、低剂量当归组及高剂量当归组,每组11只。通过Morris水迷宫和物体再认实验评价大鼠海马依赖的空间学习和记忆能力,并采用酶联免疫吸附法检测大鼠海马区β淀粉样蛋白(β-amyloid,Aβ)沉积,Western blot免疫印迹法检测海马区脑源性神经生长因子(BDNF)、β分泌酶1、Aβ、Tau蛋白和蛋白激酶B(Akt)/糖原合酶激酶3β(GSK3β)信号通路磷酸化水平。结果与假手术组比较,2VO组大鼠第3、4、5天逃逸潜伏期明显延长,目标象限探索时间明显缩短,优先指数显著降低,Aβ1-40、Aβ1-42、磷酸化Tau、β分泌酶1表达明显增高,Akt/GSK3β通路磷酸化水平、BDNF明显降低(P<0.05,P<0.01)。与2VO组比较,低剂量当归组和高剂量当归组第3、4、5天逃逸潜伏期明显缩短,目标象限探索时间明显延长,优先指数显著升高,Aβ1-40、Aβ1-42、磷酸化Tau、β分泌酶1表达明显降低,Akt/GSK3β通路磷酸化水平明显升高(P<0.05,P<0.01)。与低剂量当归组比较,高剂量当归组逃逸潜伏期明显缩短,目标象限探索时间明显延长。与2VO组比较,高剂量当归组海马BDNF表达明显增高(0.360±0.027 vs 0.056±0.019,P<0.01)。结论当归可能通过抑制Akt/GSK3β通路和β分泌酶1活性而抑制慢性脑低灌注大鼠海马内磷酸化Tau蛋白和Aβ沉积等阿尔茨海默病样病理变化,从而改善认知功能。

Objective To study effect of Radix Angelica Sinensis （RAS） on Alzhemier＇s Disease （AD）-like lesions in rats with chronic cerebral hypoperfusion （CCH）. Methods rats were ran- domly divided into sham group, bilateral vascular occlusion （model group）, low RAS dose treatment group and high RAS dose treatment group. Cognitive function was assessed by Morris Water Maze and Object Recognition Test. Aβ was detected by ELISA while brain-derived neurotrophic factor （BDNF）、β secretory enzyme 1 （BACE1）.phosphorylated Tau and phosphorylation of Akt/ GSK3β was detected by Western blot. Results There were shorter target quadrant exploration time （TQET）, lower priority index （PI）. phosphorylated Akt/GSK3β expression.BDNF and higher Aβ1-40 、Aβ1-42 、p-Tau and BACE1 in model group than in sham group （P〈0.05 ,P〈0.01）. Low and high RAS dose treatment lengthened TQET, improved PI、phosphorylated Akt/GSK3β expression and BDNF while decreased Aβ1-40 、Aβ1-42、p-Tau and BACE1 compared with model group. BDNF was higher after high dose RAS treatment than model group （P〈0.01）. Conclusion RAS inhibits AD-like lesions in rats with CCH by downregulating the Akt/GSK3β pathway and BACE1 activity,thus improving the cognitive impairment.