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- 2016
姜黄素和脑源性神经营养因子对阿尔茨海默病记忆的改善作用
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Abstract:
摘要：目的 研究姜黄素对阿尔茨海默病(Alzheimer’s disease, AD)模型大鼠学习记忆能力的影响及其作用机制。方法 采用脑室内注射Aβ1-42的方法，制备AD动物模型。单次腹腔注射(急性治疗组)或连续6d腹腔注射(慢性治疗组)50、100、300mg/kg剂量的姜黄素，结合海马内微量注射脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)(每侧1.0μg)、BDNF shRNA慢病毒(每侧2.0×105单位)，分析大鼠Y迷宫、Morris水迷宫及旷场行为变化，并应用Western blot检测海马BDNF表达变化。结果 姜黄素急性治疗对AD模型大鼠自主改变行为、总活动距离、水迷宫潜伏期没有显著作用。300mg/kg姜黄素慢性治疗后AD大鼠自主改变行为(P<0.0001)及在水迷宫测试中记忆能力(P<0.05)比盐水对照组显著增高。100和300mg/kg姜黄素慢性治疗组海马BDNF表达和盐水对照组相比显著上升(P分别<0.05和<0.0001)。海马内注射BDNF的AD大鼠水迷宫潜伏期显著下降(F4,295=5.813，P<0.01)。姜黄素慢性治疗+shBDNF组大鼠在2号象限内的游泳时间与盐水对照组无差异(P=0.657)，而100mg/kg姜黄素组、BDNF组、假手术组大鼠的停留时间比盐水对照组显著增高(P值分别<0.05、<0.05、<0.0001)。结论 姜黄素可能通过上调BDNF的表达继而激活下游信号通路，最终对Aβ诱导的AD大鼠学习记忆能力起到改善作用。
ABSTRACT: Objective To study the effect of curcumin on the learning and memory ability in a rat model of Alzheimer’s disease (AD). Methods AD rat model was prepared using intraventricular injection of Aβ1-42. Curcumin was acutely (single injection before the behavioral tests) or chronically (injected for 6 consecutive days) injected intraperitoneally at doses of 50, 100 or 300mg/kg. Brain-derived neurotrophic factor (BDNF) protein (1μg/side) or BDNF shRNA (2×105 units/side) was infused into the hippocampus. The behavioral changes in Y-maze, open field test and Morris water maze and the expression of BDNF in the hippocampus were analyzed. Results Acute treatment with curcumin had no significant effects on the spontaneous alteration, locomotor activity or water maze latency of AD rats. AD rats treated chronically with curcumin (300mg/kg) showed significant elevation in the spontaneous alternation (P<0.0001) in Y-maze and memory ability in the water maze test (P<0.05) compared with those in the saline group. Chronic treatment with 100 and 300mg/kg of curcumin induced an increased level of BDNF in the hippocampus as compared with the saline controls (P<0.05 and <0.0001). Intrahippocampal injection of BDNF significantly decreased the escape latency of AD rats in the water maze (F4,295=5.813, P<0.01). Rats chronically injected with curcumin combined with shBDNF showed no difference in the swimming time in Ⅱ quadrant as compared with saline controls (P=0.657). However, rats in 100mg/kg curcumin group, BDNF group and sham group had significantly increased swimming time than the saline controls (P<0.05, P<0.05 and P<0.0001, respectively). Conclusion Curcumin may activate the downstream signaling pathways by upregulating the expression of BDNF and ultimately contribute to the improvement of learning and memory in AD rats
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