阿尔茨海默病病程与炎症因子相关性及多奈哌齐对重症阿尔茨海默病治疗作用的研究OA
Association between the course of Alzheimer disease and inflammatory factors and the therapeutic effect of done-pezil on severe Alzheimer disease
目的 探讨阿尔茨海默病模型小鼠炎症因子、mTOR信号通路表达水平及与病程的相关性;探讨多奈哌齐片对重症阿尔茨海默病模型鼠的治疗作用.方法 通过向 8 周龄 C57BL6 小鼠腹腔注射不同剂量(60 mg/kg、120 mg/kg、180 mg/kg)D-半乳糖诱导轻、中、重度阿尔茨海默病的发生,180 mg/kg D-半乳糖组小鼠给予多奈哌齐片5 mg/kg灌胃,作为治疗组.行为学实验(水迷宫、Y迷宫、新事物认知实验)检测各组小鼠行为认知能力改变;Western blotting检测各组小鼠体内mTOR信号通路相关蛋白的表达;ELISA实验检测各组小鼠外周血炎症因子IL-6、IL-1β、TNF-α的表达;Pearson检验检测各组小鼠炎症因子与病程的相关性.结果 行为学实验结果显示,与对照组相比,各模型组小鼠均存在不同程度的认知功能损害(P<0.05),多奈哌齐治疗组对此有逆转作用(P<0.05).Western blotting结果显示,各模型组小鼠mTOR信号通路均存在不同程度的异常激活(P<0.05),且随D-半乳糖剂量的增加,其激活程度有所增加,但不具有统计学意义(P>0.05),多奈哌齐治疗组可逆转此种异常激活(P<0.05).ELISA实验显示,各模型组小鼠外周血炎症因子IL-6、IL-1β、TNF-α的表达均异常增高(P<0.05),且随D-半乳糖剂量的增加,其激活程度有所增加,其中IL-6、TNF-α的表达与D-半乳糖的使用剂量呈正相关.结论 阿尔茨海默病模型小鼠体内mTOR信号通路被异常激活,炎症因子水平异常增高,炎症因子升高水平与病程具有相关性,多奈哌齐对重症阿尔茨海默病小鼠有治疗效果.
Objective To investigate the expression levels of inflammatory factors and the mTOR signaling pathway in a mouse model of Alzheimer disease and their association with the course of the disease,as well as the therapeutic effect of donepezil in mice with severe Alzheimer disease.Methods C57BL6 mice,aged 8 weeks,were given intraperitoneal injection of different doses(60,120,and 180 mg/kg)of D-galactose to induce mild,moderate,and severe Alzheimer dis-ease,and the mice in the 180 mg/kg D-galactose group were given Aricept by gavage at a dose of 5 mg/kg as the treatment group.Behavioral experiments(water maze,Y maze,and novel object recognition test)were used to observe the change in cognitive ability;Western blotting was used to measure the expression levels of proteins associated with the mTOR sig-naling pathway;ELISA was used to measure the expression levels of the peripheral blood inflammatory factors interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α);the Pearson test was used to investigate the cor-relation between inflammatory factors and the course of the disease in each group.Results The behavioral experiments showed that compared with the control group,the mice in each model group had different degrees of cognitive impairment(P<0.05),and donepezil treatment could reverse such changes(P<0.05).Western blotting showed varying degrees of abnormal activation of the mTOR signaling pathway in each model group(P<0.05),and the degree of activation increased with the increase in the dose of D-galactose(P>0.05);donepezil treatment could reverse such changes(P<0.05).ELISA showed that there were abnormal increases in the expression levels of the peripheral blood inflammatory factors IL-6,IL-1β,and TNF-α in each model group(P<0.05),and the increases in these factors increased with the dose of D-galactose;the expression levels of IL-6 and TNF-α were positively correlated with the dose of D-galactose.Conclusion The mTOR signaling pathway is abnormally activated in mice with Alzheimer disease,with abnormal in-creases in the levels of inflammatory factors,and the increases in inflammatory factors are associated with the course of the disease.Aricept has a therapeutic ef-fect in mice with severe Alzheimer disease.
刘福荣;唐超;舒敏;王佳良;沈男男
绍兴大学附属医院药剂科,浙江 绍兴 312000浙大城市学院医学院,浙江 杭州 310015浙大城市学院医学院,浙江 杭州 310015绍兴大学附属医院药剂科,浙江 绍兴 312000绍兴大学附属医院药剂科,浙江 绍兴 312000
医药卫生
阿尔茨海默病炎症因子相关性mTOR信号通路多奈哌齐
Alzheimer diseaseInflamma-tory factorsCorrelationThe mTOR signaling pathwayDonepezil
《中风与神经疾病杂志》 2026 (5)
457-462,6
国家自然科学基金(31801207)绍兴市卫生健康科技计划(2024SKY073)浙江省药学会药品临床综合评价专项科研资助项目(2024ZYYL17)
评论