蒙花苷对APP/PS1小鼠Aβ沉积和神经炎症的作用  

Pharmacological effects of linarin on Aβ deposition and neuroinflammation in APP/PS1 mice

作　　者：毛佩芝 严荧燕 严增泽 戚建华[2] 王龙虎[2] 陈琦君[3] MAO Pei-zhi;YAN Ying-yan;YAN Zeng-ze;QI Jian-hua;WANG Long-hu;CHEN Qi-jun(Women and Children’s Hospital of Ningbo University,Ningbo Zhejiang 315012,China;College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;the Affiliated Kangning Hospital of Ningbo University,Ningbo Zhejiang 315201,China)

机构地区：[1]宁波大学附属妇女儿童医院,浙江宁波315012 [2]浙江大学药学院,浙江杭州310058 [3]宁波大学附属康宁医院,浙江宁波315201

出　　处：《中国药理学通报》2025年第4期661-667,共7页Chinese Pharmacological Bulletin

基　　金：国家重点研发计划项目(No.2022YFE0104000);宁波市公益性科技计划项目(No.2022S088);宁波市医学重点扶植学科(No.2022-F26)。

摘　　要：目的考察蒙花苷改善阿尔茨海默病(Alzheimer’s disease,AD)动物模型小鼠认知行为能力,探究其治疗Aβ沉积和神经炎症两个核心病理特征的效果以及关联性。方法APP/PS1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,TUNEL法检测小鼠CA1区组织神经元凋亡,IHC检测小鼠脑组织Aβ42、GFAP的蛋白表达水平,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NCP较少、目标象限行程较短、目标象限停留时间百分比较低(P均<0.01),海马CA1区组织细胞凋亡率较高(P<0.01),Aβ42、GFAP的蛋白表达明显较高(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NCP较多、目标象限的行程较长、目标象限停留时间百分比较高(P均<0.05),海马CA1区组织细胞凋亡率较低(P<0.01),Aβ42、GFAP的蛋白表达明显较低(P均<0.01),BACE1和PS-1蛋白表达明显较低(P均<0.01)。结论蒙花苷能抑制Aβ形成的两个关键酶从而减少APP裂解与Aβ42的生成,抑制星形胶质细胞的活化,缓解神经炎症,改善AD核心病理特征,从而改善APP/PS1小鼠学习记忆能力。Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on Aβdeposition and neuroinflammation and its correlation.Methods APP/PS1 transgenic mice were randomly divided into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and memory abilities of mice.TUNEL staining was used to detect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Compared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P<0.01),higher apoptosis rate of neurons in the CA1 region(P<0.01),significantly higher protein expression levels of Aβ42 and GFAP(all P<0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P<0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer target quadrant travel,more target quadrant residence time percentage(all P<0.05),lower apoptosis rate of neurons in the CA1 region(P<0.01),significantly lower protein expression levels of Aβ42 and GFAP(all P<0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P<0.01).Conclusions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of Aβ42,thereby inhibiting the activation of astrocytes,alleviating neuroinflammation,improving the core pathological features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

关 键 词：蒙花苷 阿尔茨海默病 APP/PS1 认知行为 AΒ沉积 神经炎症 

分 类 号：R-332[医药卫生] R284.1R322.81R338.64R745.7