摘要
目的探究姜黄素干预APP/PS1双转基因小鼠阿尔茨海默症(AD)进程的机制。方法选择7月龄雄性APP/PS1双转基因小鼠随机分为模型组和姜黄素干预组,每组6只;及同窝对照小鼠6只。姜黄素组小鼠每天腹腔注射1次姜黄素(200mg/kg),模型组与对照组腹腔注射等量生理盐水。连续注射6天,期间进行Morris水迷宫衡量小鼠的空间感知和记忆能力;第7天将各组小鼠处死取脑,HE染色观察脑组织病理情况;TUNEL检测海马CA1,CA3区凋亡细胞数;Westernblot检测海马组织Aβ、APP、p-Tau(Ser396)、NLRP3、caspase-1、cleaved-caspase-1、GasdermiD和cleaved-GasdermiD的蛋白表达。结果姜黄素处理能缩短AD小鼠潜伏期,增加穿越平台次数与原象限滞留时间;减轻AD小鼠海马组织炎性病变,降低海马神经细胞凋亡率,降低海马组织AD相关蛋白Aβ、APP、P-Tau(Ser396)蛋白表达、降低焦亡相关蛋白NLRP3、cleaved-caspase-1和cleaved-GasdermiD蛋白表达、上调caspase-1和GasdermiD蛋白表达。结论姜黄素能够通过NLRP3/caspase-1/GasdermiD轴改善APP/PS1双转基因小鼠阿尔茨海默症的空间认知障碍,减轻海马神经元损伤。
Objective To explore the mechanism of curcumin intervention in the progression of Alzheimer's disease(AD)in APP/PS1 double transgenic mice.Methods Seven-month-old male APP/PS1 double transgenic mice were randomly divided into model group and curcumin intervention group,with 6 mice in each group;and 6 mice in the same litter as control.The mice in the curcumin group were intraperitoneally injected with curcumin(200mg/kg)once a day,while the mice in the model group and control group were intraperitoneally injected with the same amount of saline.After 6 consecutive days of injection,the spatial perception and memory ability of the mice were measured by morris water maze.On the 7th day,the rats in each group were sacrificed and the brains were removed for observation of the pathological conditions of brain tissues;TUNEL was used to detect the number of apoptotic cells in hippocampal CA1 and CA3 regions;Western blot was used to detect the protein expressions of Aβ,APP,P-Tau(Ser396),NLRP3,caspase-1,cleaved-caspase-1,Gasdermi D and cleaved-Gasdermi D in hippocampus.Results Curcumin treatment could shorten the latency of AD mice,increase the number of times crossing the platform and the original quadrant retention time;alleviate the inflammatory lesions of hippocampal tissues in AD mice,reduce the apoptosis rate of hippocampal nerve cells,reduce the protein expressions of AD-related proteins Aβ,APP and p-Tau(Ser396)in hippocampus,reduce the protein expressions of pyroptosis-related proteins NLRP3,cleaved-caspase-1 and cleaved-Gasdermi D,and up-regulate the protein expressions of caspase-1 and Gasdermi D.Conclusion Curcumin can improve the spatial cognitive impairment of APP/PS1 double transgenic mice with AD through the NLRP3/caspase-1/Gasdermi D axis,and reduce the hippocampal neuron damage.
作者
李振宇
王雪
王艳方
LI Zhen-yu;WANG Xue;WANG Yan-fang(Department of Anesthesiology,Shandong Provincial Third Hospital,Jinan 250031,China;Department of Pathology,Third Affiliated Hospital of Shandong First Medical University,Jinan 250031,China;Department of Anesthesiology,Fourth People's Hospital of Jinan City,Jinan 250031,China)
出处
《解剖科学进展》
CAS
2024年第1期25-28,共4页
Progress of Anatomical Sciences
