芝麻素对AD模型小鼠学习和记忆能力的影响及其机制

doi:10.13481/j.1671-587x.20190614

摘要/Abstract

摘要： 目的：观察芝麻素对阿尔茨海默病（AD）模型小鼠学习记忆和能力的影响，阐明其可能的作用机制。方法：40只C57BL/6雄性小鼠随机分为对照组、模型组、吡拉西坦组、低剂量芝麻素组和高剂量芝麻素组，每组8只。除对照组外其他各组小鼠采用侧脑室注射淀粉样β蛋白片段25-35（Aβ_25-35）的方法建立AD模型，24 h后，吡拉西坦组小鼠给予吡拉西坦灌胃，低和高剂量芝麻素组小鼠分别给予50和100 mg·kg^-1芝麻素灌胃，对照组和模型组小鼠给予等量的生理盐水。采用Morris水迷宫实验观察各组小鼠逃避潜伏期、小鼠在目标象限游程和目标象限停留时间，流式细胞术检测各组小鼠脑组织中活性氧（ROS）水平，ELISA法检测小鼠脑组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）水平，Western blotting法检测各组小鼠脑组织中凋亡相关蛋白B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）和含半胱氨酸的天冬氨酸蛋白水解酶3（Caspase-3）蛋白表达水平。结果：与对照组比较，模型组小鼠逃避潜伏期明显延长（P<0.05），目标象限游程和目标象限停留时间明显缩短（P<0.05）；与模型组比较，吡拉西坦组、低剂量芝麻素组和高剂量芝麻素组小鼠逃避潜伏期明显缩短（P<0.05），目标象限游程和目标象限停留时间增加（P<0.05）。与对照组比较，模型组小鼠脑组织中ROS和MDA水平明显升高（P<0.05），SOD活性明显降低（P<0.05），Bax和Caspase-3蛋白表达水平明显升高（P<0.05），Bcl-2蛋白表达水平和Bcl-2/Bax比值明显降低（P<0.05）；与模型组比较，吡拉西坦组、低和高剂量芝麻素组小鼠脑组织中ROS和MDA水平明显降低（P<0.05），SOD活性明显升高（P<0.05），Bax和Caspase-3蛋白表达水平明显降低（P<0.05），Bcl-2蛋白表达水平和Bcl-2/Bax比值明显升高（P<0.05）。结论：芝麻素可能通过提高神经元抗氧化能力、抑制神经元凋亡而提高AD模型小鼠的学习和记忆能力。

关键词: 芝麻素, 阿尔茨海默病, 学习记忆, 氧化应激, 凋亡相关蛋白

Abstract: Objective: To observe the effects of sesamin on the abilities of learning and memory in the mice with Alzheimer's disease (AD), and to elucidate their possible mechanisms. Methods: Forty male C57BL/6 mice were randomly divided into control, model, piracetam, low dose of sesamin, and high dose of sesamin groups, and there were 8 mice in each group. The AD models were established by intracerebroventricular injection of amyloid β-protein fragment 25-35 (Aβ_25-35) in the mice in the other groups except control group. 24 h later, the mice in piracetam group were intragastrically administed with piracetam; the mice in low and high doses of sesamin groups were intragastrically administrated of 50 and 100 mg·kg^-1 sesamin, respectively; the mice in control and model groups were intragastrically administrated with the same amount of normal saline once a day for 2 weeks. Morris water maze test was used to observe the escape latencies,the swimming distance and the resident time in target quadrant of the mice in various groups;flow cytometry was used to detect the level of active oxygen(ROS) in brain tissue of the mice in various groups;ELISA was used to detect the activities of superoxide dismutase (SOD) and levels of malondialdehyde (MDA) in brain tissue of the mice in various groups; Western blotting was used to determine the expression levels of apoptosis-related protein B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate specific proteinase-3 (Caspase-3) proteins in brain tissue of the mice in various groups. Results: Compared with control group,the escape latency of the mice in model group was significantly prolonged (P<0.05), and the swimming distance and the resident time in target quadrant were significantly shortened (P<0.05); compared with model group,the escape latencies of the mice in piracetam group, low dose of sesamin group and high dose of sesamin group were significantly shortened (P<0.05), and the swimming distance and the resident time in target quadrant were significantly increased (P<0.05). Compared with control group, the levels of ROS and MDA in brain tissue of the mice in model group were significantly increased (P<0.05), the SOD activity was significantly decreased (P<0.05), the expression levels of Bax and Caspase-3 protein were significantly increased (P<0.05), and the expression level of Bcl-2 protein and the value of Bcl-2/Bax were significantly decreased (P<0.05); compared with model group, the levels of ROS and MDA in brain tissues of the mice in piracetam, low dose of sesamin, and high dose of sesamin groups were significantly decresed (P<0.05), the activities of SOD were significantly increased (P<0.05), the expression levels of Bax and Caspase-3 proteins were significantly decresed (P<0.05), and the expression levels of Bcl-2 protein and the values of Bcl-2/Bax were significantly increased (P<0.05). Conclusion: Sesamin may improve the learning and memory abilities of the AD model mice by increasing the neuronal antioxidant capacity and inhibiting the neuronal apoptosis.

Key words: sesamin, Alzheimer’s disease, learning and memory, oxidative stress, apoptosis-related proteins

中图分类号:

R749.16

李金花, 金颖, 李俊峰, 李莉. 芝麻素对AD模型小鼠学习和记忆能力的影响及其机制[J]. 吉林大学学报(医学版), 2019, 45(06): 1275-1280.

LI Jinhua, JIN Ying, LI Junfeng, LI Li. Effects of sesamin on abilities of learning and memory in AD model mice and their mechanisms[J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1275-1280.

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