还脑益聪方对老年认知障碍大鼠学习记忆及脑组织β淀粉样蛋白和Tau蛋白表达的影响

摘要

目的：探讨补肾益气、活血解毒中药-还脑益聪方颗粒剂对认知功能障碍的自然衰老大鼠学习记忆功能及脑组织β淀粉样蛋白及Tau蛋白等表达的影响。方法以Morris水迷宫试验检测SD老年大鼠的空间学习记忆能力，将学习记忆减退的50只老年大鼠结合体质量，分层随机方法分成为模型（老年认知障碍）对照组、阳性对照药（盐酸多奈哌齐片，0.49 mg／kg）组、还脑益聪颗粒剂小剂量（3.78 g 生药／kg）组、中剂量（7.56 g生药／kg）组、大剂量（18.90 g生药／kg）组，每组10只，学习记忆能力正常老年大鼠10只为老年正常对照组给予等量水，连续灌胃14 w。给药结束后，行Morris水迷宫试验，测试老年大鼠空间学习记忆能力，免疫组织化学方法观察海马组织CA1区早老蛋白-1（ PS-1）、β淀粉样肽和 Tau蛋白激酶（TTBK1）的表达，积分光密度值（IOD）。结果与正常组比较，模型组老年大鼠穿台次数显著减少（P＜0.05），第四象限游泳路程显著缩短（P＜0.01）。给药14 w后，还脑益聪方各剂量组第四象限游泳路程显著延长（P＜0.01），还脑益聪方大剂量组第四象限游泳时间显著延长（P＜0.05）。模型组老年大鼠海马CA1区TTBK1阳性表达明显增多，PS-1表达水平增强，β淀粉样沉积增多。经治疗后，TTBK1、PS-1和β淀粉样肽的阳性表达明显减少，和模型组比较差异均具有统计学意义（P＜0.05，P＜0.01）。结论还脑益聪方可抑制脑组织β淀粉样蛋白和Tau蛋白的沉积，保护脑组织海马形态的完整性，从而改善老年认知障碍大鼠空间学习记忆能力。%Objective To observe the effects of Huannao Yicong decoction ( HYD) on learning and memory function , the expres-sions of β-amyloid(Aβ) protein and TTBK1 in aging rats with cognitive impairment .Methods Morris water maze test was used to measure the spatial learning and memory of SD aging rats .50 aging rats with learning and memory impairment combining with weight were divided randomly into model(aged rats with cognitive impairment), positive control(Hydrochloric donepezil Tablets, 0.49 mg/kg), HYD granules small-dose(3.78 g crude drug/kg), middle-dose (7.56 g crude drug/kg), big-dose groups (15.12 g crude drug/kg), 10 in each group. The learning and memory capacity was tested by Morris water maze .The expressions of PS-1, Aβprotein and TTBK1 in hippocampus organi-zation CA1 region were detected by immunohistochemical method .Results Comparing with those of normal aged rats group , the number of model group aged rats passing the platform and the swimming distance in the fourth quadrant were significantly decreased ( P<0 .01 ) .After 14 weeks treatment, the swimming distance in the fourth quadrant of each HYD group were significantly increased (P<0.01), the swimming time in the fourth quadrant of big-dose group was significantly increased (P<0.05).The expressions of PS-1, TTBK1 andβ-amyloid protein were significantly increased in hippocampus CA1 area of the model groups.After treatment, the expressions of PS-1, TTBK1 andβ-amyloid proteins were significantly decreased (P<0.05,P<0.01).Conclusions HYD could reduce the deposition of Aβprotein and TTBK1 in brain tissue, protect the integrity of histomorphology in the hippocampus , and thus improve the spatial learning and memory capacity of aged rats with cognitive impairment .