摘要
目的观察丁苯酞(NBP)软胶囊对阿尔茨海默病(AD)模型大鼠海马CA1区丝氨酸蛋白激酶-3β(GSK-3β)、p-Tau蛋白表达的影响,探讨NBP治疗AD的机制。方法将72只雄性SD大鼠随机分为假手术组(24只)、AD模型组(24只)、NBP治疗组(24只)。采用β-淀粉样蛋白1-42(Aβ1-42)制作AD模型,假手术组注射5μL生理盐水。造模成功后4周,NBP治疗组给予NBP与食用油混合后制成的NBP混合溶液灌胃;假手术组和AD模型组采用同等剂量的食用油进行灌胃。采用Morris水迷宫实验比较各组大鼠穿越平台次数。采用Western blot法分别于给药后1、2、4和8周检测海马CA1区GSK-3β、p-Tau蛋白的表达情况。结果与假手术组比较,AD模型组大鼠各时间点穿越平台次数显著减少(均P<0.05);与AD模型组比较,NBP治疗组各时间点大鼠穿越平台次数均增加(均P<0.05);与假手术组同期比较,AD模型组大鼠海马CA1区p-Tau、GSK-3β蛋白相对表达水平升高,差异有高度统计学意义(P<0.01);与AD模型组同期比较,NBP治疗组大鼠海马CA1区p-Tau、GSK-3β蛋白相对表达水平降低,差异有高度统计学意义(P<0.01);与假手术组同期比较,NBP治疗组大鼠海马CA1区p-Tau、GSK-3β蛋白相对表达水平升高,差异有高度统计学意义(P<0.01)。结论NBP可通过下调GSK-3β、p-Tau蛋白的表达,发挥对AD模型大鼠的脑保护作用。
Objetive To observe the effects of Butylphthalide(NBP)on the expression of glycogen synthase kinase-3β(GSK-3β)protein and p-Tau protein in CA1 region of hippocampus of Alzheimer′s disease rats,and to explore the mechanism of brain protection by butylphthalide.Method Seventy-two male SD rats were randomly divided into sham operation group(24 rats),AD model group(24 rats)and NBP treatment group(24 rats).Aβ-amyloid 1-42(Aβ1-42)was used to make AD model.The sham operation group was injected with 5μL saline.Four weeks after successful modeling,NBP treatment group was given NBP mixed solution made of NBP and edible oil by gavage.The sham operation group and the AD model group were given the same dose of edible oil.Morris water maze experiment was used to compare the number of times the rats crossed the platform.Western blot was used to detect the expression of GSK-3βand p-Tau proteins in the hippocampal CA1 region at one,two,four and eight weeks after administration.Results Compared with the sham operation group,the number of rat crossing the platform at each time point in AD model group was significantly reduced(all P<0.05).Compared with AD model group,the number of rats crossing the platform increased at each time point in the NBP treatment group(all P<0.05).Compared with the sham operation group in the same period,the relative expression levels of p-Tau and GSK-3βproteins in the hippocampal CA1 area of the AD model group were increased,and the differences were highly statistically significant(P<0.01).Compared with the AD model group in the same period,the relative expression levels of p-Tau and GSK-3βproteins in the hippocampal CA1 area of rats in the NBP treatment group were decreased,and the differences were highly statistically significant(P<0.01).Compared with the sham operation group in the same period,the relative expression levels of p-Tau and GSK-3βproteins in the hippocampal CA1 area of rats in the NBP treatment group were increased,and the difference was statistically significant(P<0.01).Conclusion NBP can play a protective role on the brain of AD model rats by down-regulating the expression of GSK-3βand p-Tau protein.
作者
邓春颖
李海滨
毛文静
李世英
DENG Chunying;LI haibin;MAO Wenjing;LI Shiying(Department of Neurology,North China University of Science and Technology Affiliated Hospital,Hebei Province,Tangshan 063000,China;Department of Cardiology,People′s Hospital of Zunhua,Hebei Province,Zunhua 064200,China)
出处
《中国医药导报》
CAS
2020年第27期16-19,共4页
China Medical Herald
基金
河北省重点研发计划自筹项目(172777151)
华北理工大学科学研究基金项目(Z201734)。
作者简介
通讯作者:李世英(1970.11-),女,硕士,主任医师,研究方向:脑血管病、阿尔茨海默症、神经系统免疫疾病等。
