丁苯酞对阿尔茨海默病模型大鼠海马CA1区p38丝裂原活化蛋白激酶和核因子κB以及白细胞介素1β表达的影响  

Effect of butylphthalideon on the expression of p38 mitogen activatedprotein kinase,nuclear factorκB and interleukin 1βin CA1 region of hippocampus of Alzheimer's disease rats

作　　者：邓春颖 李海滨[2] 毛文静 李世英 刘昊 Deng Chunying;Li Haibin;Mao Wenjing;Li Shiying;Liu Hao(Department of Neurology,the Affiliated Hospital of North China University of Science and Technology,Hebei Province,Tangshan 063000,China;Department of Cardiology,People's Hospital of Zunhua,Hebei Province,Zunhua 064200,China)

机构地区：[1]华北理工大学附属医院神经内科,河北省唐山市063000 [2]河北省遵化市人民医院心内科,064200

出　　处：《中国医药》2020年第6期873-877,共5页China Medicine

基　　金：河北省重点研发计划(172777151);华北理工大学科学研究基金项目(Z201734)。

摘　　要：目的探讨丁苯酞对阿尔茨海默病(AD)模型大鼠学习记忆能力和海马CA1区p38丝裂原活化蛋白激酶(p38 MAPK)、核因子κB、白细胞介素1β(IL-1β)表达的影响。方法选择健康清洁级雄性SD大鼠72只,采用随机数字表法分为假手术组、AD模型组、丁苯酞组,各24只。假手术组不造模给予食用油灌胃;AD模型组大鼠双侧海马CA1区注射β淀粉样蛋白1-42造模后给予食用油灌胃;丁苯酞组造模后给予丁苯酞和食用油混合溶液灌胃。采用Morris水迷宫实验比较各组大鼠给药1、2、4、8周的逃避潜伏期,应用蛋白质印迹法检测大鼠脑组织海马CA1区p38 MAPK、核因子κB、IL-1β蛋白的表达。结果给药1、2、4、8周,AD模型组、丁苯酞组逃避潜伏期均长于假手术组,给药8周,丁苯酞组逃避潜伏期短于AD模型组[(60.5±1.1)s比(76.8±1.1)s],差异均有统计学意义(均P<0.001)。给药1、2、4、8周,假手术组大鼠海马CA1区可见少量p38 MAPK、核因子κB、IL-1β蛋白表达,与假手术组比较,AD模型组各时点p38 MAPK、核因子κB、IL-1β蛋白表达明显增多;与AD模型组比较,丁苯酞组各时点p38 MAPK、核因子κB、IL-1β蛋白表达明显减少,差异均有统计学意义(均P<0.01)。结论丁苯酞能改善AD大鼠的学习记忆能力从而发挥脑保护作用,具体机制可能是通过下调p38 MAPK、核因子κB、IL-1β的活性而实现的。Objective To investigate the effects of butylphthalide on learning and memory abilities and mitogen activatedprotein kinase(MAPK),nuclear factorκB(NF-κB)and interleukin1β(IL-1β)expression at CA1 region in hippocampus of rats with Alzheimer's disease.Methods Totally 72 SD healthy and clean grade rats were randomly divided into the sham-operation group,the Alzheimer's disease model group(AD group)and the butylphthalide treated group(NBP group),with 24 rats in each group.In sham-operation group,rats were gavaged with cooking oil without modeling;in AD group,the AD rat models were prepared by injecting beta-amyloid 1-42 into bilateral hippocampal CA1 areas and gavaged with cooking oil;in NBP group,rats were gavaged with a mixture of butylphthalide and cooking oil after modeling.Morris water maze experiment was used to analyze the escape latency of rats in each group at 1,2,4 and 8 weeks after administration.Western blot was used to detect the expression of p38 MAPK,NF-κB and IL-1β,at CA1 region in hippocampus of rats brain tissues.Results At 1,2,4 and 8 weeks,the escape latency of AD group and NBP group was longer than that of sham-operation group.At 8 weeks,the escape latency of NBP group was shorter than that of AD group[(60.5±1.1)s vs(76.8±1.1)s];the difference was statistically significant(all P<0.05).A small amount of p38 MAPK,NF-κB,IL-1βprotein was found in CA1 area of hippocampus of rats in sham-operation group at 1,2,4 and 8 weeks after administration.Compared with sham-operation group,the expression of p38 MAPK,NF-B,IL-1βprotein in AD group increased significantly at each time point.Compared with AD group,the expression of p38 MAPK,NF-κB,IL-1βprotein in NBP group decreased significantly at each time point(all P<0.01).Conclusions Butylphthalide can protect the brain and improve the learning and memory abilities of AD rats.The specific mechanism may be achieved by down-regulating the expression of p38 MAPK,NF-κB and IL-1.

关 键 词：阿尔茨海默病 P38丝裂原活化蛋白激酶 核因子ΚB 白细胞介素1Β 丁苯酞 

分 类 号：R741.02[医药卫生—神经病学与精神病学]