蒙花苷对阿尔茨海默病小鼠认知功能及多病理特征的影响

毛佩芝; 严荧燕; 吴燕华; 王龙虎; 戚建华; 陈琦君

doi:10.13748/j.cnki.issn1007-7693.20241926

蒙花苷对阿尔茨海默病小鼠认知功能及多病理特征的影响

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

摘要

摘要:
目的考察蒙花苷改善阿尔茨海默病(Alzheimer’s disease，AD)小鼠认知行为能力的作用，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、阳性对照组和蒙花苷高、中、低剂量组，C57BL/6J小鼠为正常组。Morris水迷宫试验检测学习记忆能力，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、Ach含量及炎症因子TNF-α、IL-1β表达水平，Western blotting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、穿越目标次数较少、逃避潜伏期较长(P<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<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<0.01)，BACE1和PS-1蛋白表达水平也明显较高(P<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、穿越目标次数较多、逃避潜伏期较短(P<0.05或P<0.01)，Aβ42、GFAP、P-tau Ser396、P-tau Ser404的蛋白表达显著较低(P<0.05或P<0.01)，Ach含量明显较高(P<0.05或P<0.01)，而AchE以及TNF-α、IL-1β明显较低(P<0.01)，BACE1和PS-1蛋白表达明显较少(P<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，发挥改善AD多病理特征的效应。

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 model group, positive control group, and high-, medium-, low-dose linarin group, with C57BL/6J mice serving as the control 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 blotting was performed to measure the protein expression levels of BACE1 and PS-1 in brain tissue.
RESULTS Compared with the control group, the model group exhibited significantly shorter residence time in the target quadrant, lower target-zone frequency, and longer escape latency(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 (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(P<0.01). The protein expression levels of BACE1 and PS-1 were also significantly increased(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 target-zone frequency, and shorter escape latency(P<0.05 or P<0.01). The protein expression levels of Aβ42, GFAP, P-tau Ser396, and P-tau Ser404 were significantly decreased (P<0.05 or P<0.01), while the Ach content was significantly increased(P<0.05 or P<0.01). Additionally, AchE activity and the protein levels of TNF-α and IL-1β were significantly decreased(P<0.01), along with significant decrease in BACE1 and PS-1 protein expression(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 therapeutic effect on improving multiple pathological features of AD by eliminating brain inflammation, inhibiting β-amyloid aggregation, and reducing Tau protein hyperphosphorylation.

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