蒙花苷对阿尔兹海默症小鼠认知功能以及多病理特征的影响

Investigation of the Effects of Linarin on the Cognitive Abilities and Multiple Pathological Features of Alzheimer's Disease Mice

关键词:  蒙花苷  阿尔兹海默症  认知行为  病理特征  综合治疗

Key words:  linarin  Alzheimer"s disease  cognitive behavior  pathological features  comprehensive therapeutic

摘要:

摘要：目的 考察蒙花苷改善AD小鼠认知行为能力，探究其综合治疗AD多病理特征的效果。方法 APP/PS1转基因小鼠随机分为模型组、蒙花苷高、中、低剂量组、阳性对照组，C57BL/6J小鼠为正常组。Morris水迷宫检测学习记忆能力，HE染色观察海马区病理变化，IHC检测小鼠脑组织Aβ42、GFAP、P-tau ser396、P-tau ser404的蛋白表达水平，ELISA检测脑组织AchE活性和Ach含量，以及炎症因子TNF-α、IL-1β蛋白水平，Western Blot检测小鼠脑组织BACE1和PS-1蛋白表达水平。结果 与正常组相比，模型组小鼠目标象限滞留时间较短、NCP较少、PLA较长（P均<0.01），海马CA区神经细胞形态不规则，排列紊乱，且有细胞变性与坏死，Aβ42、GFAP、P-tau ser396、P-tau ser404的蛋白表达明显较高（P均<0.01），Ach含量明显较低（P<0.01），而AchE以及TNF-α、IL-1β明显较高（P均<0.01），BACE1和PS-1蛋白表达水平也明显较高（P均<0.01）；与模型组相比，蒙花苷中高剂量组及阳性对照组小鼠目标象限滞留时间较长、NCP较多、PLA较短（P均<0.05），Aβ42、GFAP、P-tau ser396、P-tau ser404的蛋白表达显著较低（P均<0.05），Ach含量明显较高（P均<0.05），而AchE以及TNF-α、IL-1β显著较低（P均<0.01），BACE1和PS-1蛋白表达显著较少（P均<0.01）。结论 蒙花苷不仅能通过抑制乙酰胆碱酯酶活性，增加AD神经递质，明显改善AD小鼠学习记忆损伤，也可以通过消除脑部炎症、抑制β淀粉样蛋白聚集、减少Tau蛋白过度磷酸化作用，具有改善AD多病理特征的效果。

Abstract:

ABSTRACT: OBJECTIVE To investigate the effect of linarin on improving cognitive and behavioral abilities in Alzheimer's disease (AD) model mice so as to explore its comprehensive therapeutic effect on the multiple pathological features of AD. METHODS APP/PS1 transgenic mice were randomly divided into a model group, high-dose, medium-dose, and low-dose linarin groups, and a positive control group, with C57BL/6J mice serving as the normal group. The Morris water maze was used to evaluate the learning and memory abilities. HE staining was used to observe the pathological changes in hippocampus. IHC was used to detect the protein expression levels of Aβ42, GFAP, P-tau ser396, and P-tau ser404 in brain tissue. ELISA was employed to detect AchE activity, Ach content, and the protein levels of inflammatory cytokines TNF-α and IL-1β in brain tissue. Western Blot was performed to measure the protein expression levels of BACE1 and PS-1 in brain tissue. RESULTS Compared with the normal group, the model group exhibited significantly shorter residence time in the target quadrant, lower NCP, and longer PLA (all P<0.01). The neurons in the hippocampal CA region exhibited irregular morphology, disordered arrangement, and cell degeneration and necrosis. The protein expression levels of Aβ42, GFAP, P-tau ser396, and P-tau ser404 were significantly increased (all P<0.01), while the Ach content was significantly decreased (P<0.01). In contrast, AchE activity and the levels of TNF-α and IL-1β were significantly increased (all P<0.01). The protein expression levels of BACE1 and PS-1 were also significantly increased (both P<0.01). Compared with the model group, mice in the medium-dose and high-dose linarin groups, as well as the positive control group, demonstrated significantly longer residence time in the target quadrant, higher NCP, and shorter PLA (all P<0.05). The protein expression levels of Aβ42, GFAP, P-tau ser396, and P-tau ser404 were significantly decreased (all P<0.05), while the Ach content was significantly increased (P<0.05). Additionally, AchE activity and the protein levels of TNF-α and IL-1β were significantly decreased (all P<0.01), along with significant decrease in BACE1 and PS-1 protein expression (both P<0.01). CONCLUSION Linarin not only significantly ameliorates learning and memory impairments in AD mice by inhibiting AchE activity and increasing AD neurotransmitters, but also has a comprehensive therapeutic effect on improving multiple pathological features of AD by eliminating brain inflammation, inhibiting β-amyloid aggregation, and reducing Tau protein hyperphosphorylation.