ω-3不饱和脂肪酸DHA改善β淀粉样蛋白沉积致AD的小鼠模型记忆功能的机制研究  

The mechanism of omega-3 unsaturated fatty acid DHA onβ-amyloid-induced memory impairment in mice

作　　者：陆冰 刘洲 郑锡峰 刘广雁 林智君 陈秋萍 LU Bing;LIU Zhou;ZHENG Xifeng(Geriatrics Center,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,China)

机构地区：[1]广东医科大学附属医院老年医学中心,广东湛江524001 [2]广东医科大学附属医院神经病学研究所,广东湛江524001

出　　处：《中风与神经疾病杂志》2020年第2期108-111,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(青年基金项目)(No.81400986);“创新强校工程”科研项目(重点培育项目)(No.4CX14112G);广东医科大学科研基金(No.2018012590)。

摘　　要：目的探讨ω-3不饱和脂肪酸二十二碳六烯酸(DHA)改善β淀粉样蛋白(Aβ1-42)沉积所致阿尔茨海默病(Alzheimer’s disease,AD)的小鼠模型记忆功能的作用机制。方法采用Aβ-intrahippocampal injection法向36只小鼠脑内海马部位注射寡聚态Aβ1-42建立AD小鼠模型,随机分为假手术组(羧甲基纤维素钠灌胃)、Aβ模型组(羧甲基纤维素钠灌胃)和Aβ+DHA组(DHA灌胃)。Morris水迷宫检测小鼠的记忆功能;尼氏染色检测海马神经元的变化;ELISA法检测海马组织中肿瘤坏死因子α(TNF-α)和白细胞介素16(IL-16)的含量;Western blot检测海马组织中脑源性神经营养因子(BDNF)、干扰素-γ(IFN-γ)、核转录因子-κB(NF-κB)蛋白表达。结果与假手术组相比,Aβ模型组和Aβ+DHA组小鼠的潜伏期延长,跨越平台次数和BDNF蛋白相对表达量减少,而TNF-α和IL-16含量、IFN-γ和NF-κB蛋白表达量升高;与Aβ模型组相比,Aβ+DHA组小鼠的潜伏期缩短,跨越平台次数和BDNF蛋白表达量增加,而TNF-α和IL-16含量、IFN-γ和NF-κB蛋白表达量降低,差异均有统计学意义(P<0.05)。结论DHA可以改善Aβ1-42致AD小鼠模型记忆功能障碍,其作用机制可能与降低海马组织中TNF-α和IL-16含量,抑制IFN-γ和NF-κB蛋白表达,促进BDNF蛋白表达有关。Objective To analyze the effects of omega-3 unsaturated fatty acid DHA on memory in mice model with Alzheimer’s disease(AD).Methods Thirty-six mice were randomly divided into sham operation group(sodium carboxymethyl cellulose gavage),Aβmodel group(sodium carboxymethyl cellulose gavage)and Aβ+DHA group(DHA gavage).AD mice model were established by injecting oligomeric Aβ1-42 into the hippocampus of 36 mice by Aβ-intrahippocampal injection method.The memory function of mice were observed by Morris water maze test and the changes in hippocampal neurons of AD rats were determined by Nissl’s staining;In the hippocampus,the content of TNF-αand IL-16 were measured by ELISA and the expression of BDNF,IFN-γand NF-κB protein were detected by Western blot.Results Compared with sham operation group,prolongation of latency prolonged,the number of crossing platform and the expression of BDNF protein decreased,while TNF-αcontent,IL-16 content,IFN-γprotein expression and NF-κB protein expression increased in Aβmodel group and Aβ+DHA group.Compared with the Aβmodel group,the latency shortened,the number of crossing platform and BDNF protein expression increased,while the TNF-αcontent,IL-16 content,IFN-γprotein expression and NF-κB protein expression decreased in Aβ+DHA group,the differences were all statistically significant(P<0.05).Conclusion DHA can improve memory impairment in AD mice induced by Aβ1-42,and its mechanism may be related to decreasing the content of TNF-αand IL-16,inhibiting the expression of IFN-γand NF-κB,and promoting the expression of BDNF protein in hippocampus.

关 键 词：DHA AD模型 记忆功能 TNF-α NF-κB 

分 类 号：R749.1[医药卫生—神经病学与精神病学]