(1.北京工商大学 食品与健康学院, 北京 100048;2.天津农学院 基础科学学院, 天津 300392;3.天津农学院 食品科学与生物工程学院, 天津 300392)
(1.School of Food and Health, Beijing Technology and Business University, Beijing 100048,China;2.School of Basic Science, Tianjin Agricultural University, Tianjin 300392, China;3.College of Food Science and Bioengineering, Tianjin Agricultural University, Tianjin 300392, China)
研究白皮杉醇对阿尔茨海默病(Alzheimer's disease, AD)小鼠认知障碍的改善作用。取72只雄性昆明小鼠,随机分为6组,每组12只,即正常对照组、模型对照组、阳性对照组、白皮杉醇低、中、高剂量干预组。采用AlCl3和D-半乳糖联合诱导的方法连续干预70d,建立阿尔茨海默病小鼠模型。在造模35d开始用白皮杉醇连续干预,5周后通过Morris水迷宫实验评价小鼠的空间学习记忆能力,通过酶联免疫法(ELISA)检测小鼠海马体中Aβ1-42及TNF-α蛋白表达水平、小鼠血清超氧化物歧化酶(SOD)活力、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量并结合相对脏器指数分析白皮杉醇对AD小鼠的保护效果。研究发现,与正常组比较,模型对照组小鼠逃避潜伏期显著性增加,记忆能力显著性降低,而白皮杉醇可有效提高模型小鼠认知行为和记忆能力(P<0.01)；此外,与正常组比较,模型对照组小鼠脑组织中Aβ1-42水平及炎症因子TNF-α表达水平明显升高,小胶质细胞活化明显增加,而白皮杉醇干预组小鼠Aβ1-42、TNF-α及胶质细胞活化水平均显著降低(P<0.01)。进一步研究表明,白皮杉醇能有效提升小鼠血清SOD活力和GSH-Px水平,降低MDA含量,减轻氧化应激损伤。研究结果表明,白皮杉醇可以通过降低脑组织氧化应激及神经炎症反应,减少海马中β淀粉样蛋白的生成来改善阿尔茨海默病小鼠的认知功能障碍。
To evaluate the improvement effect of piceatannol on cognitive impairment in Alzheimer's disease (AD) mice, seventy-two male Kunming mice were randomly divided into 6 groups with 12 mice in each group, including control group, model control group, positive control group, piceatannol intervention groups (low-dose, medium-dose and high-dose). AD mice were induced by AlCl3 and D-galactose intervention for 70 d. After 5 weeks of continuous intervention with piceatannol on the 35th day of modeling, Morris water maze experiment was used to test the spatial learning and memory ability of mice. Meanwhile, the protein expression levels of Aβ1-42 and TNF-α in the hippocampus of mice were determined by ELISA method, and the activity of superoxide dismutase (SOD) and content of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in mice serum were detected. Combined with relative viscera index, the improvement effect of piceatannol on AD mice was analyzed. The results showed that the latency of escape in model control group was significantly higher than that in control group and the memory ability was significantly decreased, while piceatannol effectively improved the cognitive behavior and memory ability of AD model mice (P<0.01). Compared with control group, the levels of Aβ1-42, TNF-α and activated microglia were significantly increased in model control group, while piceatannol significantly decreased the levels of Aβ1-42, TNF-α and activated microglia (P<0.01). Moreover, piceatannol effectively increased the activities of SOD and the content of GSH-Px and reduced MDA content in mice serum, and alleviated oxidative injury. In conclusion, piceatannol can improve the cognitive function of AD mice by reducing oxidative stress, neuroinflammation and Aβ production in the hippocampus.