水飞蓟宾改善AD小鼠认知障碍及机制  

Silibinin attenuates learning and memory deficits through inflammation mechanism in intracerebroventricular-Aβ_(1-42) injected mice

作　　者：陈魁敏[1] 周恒伟[2] 邹丹[1] 金戈[1] 李欣欣[3] 张祖源 肖时芳[3] 邢爱平[4] 

机构地区：[1]沈阳医学院心理教研室,辽宁沈阳110034 [2]沈阳市苏家屯区中心医院 [3]沈阳医学院临床医学系 [4]沈阳医学院预防医学系

出　　处：《中国公共卫生》2015年第6期754-756,共3页Chinese Journal of Public Health

基　　金：辽宁省教育厅一般项目(L2014409);沈阳市科技局项目(F13-220-9-27)

摘　　要：目的探讨水飞蓟宾对阿尔茨海默病(AD)小鼠学习记忆影响及机制。方法以侧脑室注射淀粉样蛋白(Aβ)建立AD小鼠模型,50只小鼠随机分为5组,分别为假手术组、模型组、水飞蓟宾100.0、200.0 mg/kg组、多奈哌齐1.3 mg/kg(阳性对照)组,采用Y迷宫实验评价小鼠学习记忆能力;Western blot及ELISA法检测小鼠脑海马组织肿瘤坏死因子α(TNF-α)、白细胞介素(IL-β)蛋白表达量及炎症相关因子IL-6、IL-4含量。结果与假手术组比较,模型组小鼠新物体实验1、24 h优先指数[分别为(0.53±0.09)、(0.51±0.12)]降低,Y迷宫实验小鼠自发交替反应率[(0.52±0.09)%]降低(P<0.01);与模型组比较,水飞蓟宾200.0 mg/kg组小鼠1、24 h优先指数[分别为(0.67±0.11)、(0.69±0.11)]明显增加,小鼠自发交替反应率[(0.72±0.09)%]升高。与假手术比较,模型组小鼠海马组织中IL-4水平降低,脑海马TNF-α、IL-β蛋白表达量明显增加(P<0.01);与模型组比较,水飞蓟宾200.0 mg/kg组小鼠海马组织中IL-4水平升高,脑海马TNF-α、IL-β蛋白表达水平明显降低(P<0.01)。结论水飞蓟宾可改善AD模型小鼠学习记忆障碍,其机制可能与调控脑内炎症因子表达有关。Objective To investigate the effects and mechanism of silibinin on learning and memory in mice with Alzheimer＇s disease. Methods Alzheimer＇s disease model was established by intracerebroventricular injection of amy- loid protein β（ Aβ1-42 ）in 50 mice and then the mice were randomly divided into a control group,a model group,2 silibi- nin groups （100 and 200 mg/kg）, and a positive control group （1.3 mg/kg of donepezil ）. Learning and memory of the mice was evaluated with Y maze test. Western blot and enzyme-linked immunosorbent assay（ELISA） were adopted to de- tect the expressions of tumor necrosis factor alpha （ TNF-α ）, interleukin-1 beta （ IL-1β ）, interleukin-6 （ IL-6 ）, and inter- leukin-4 （ IL-4 ）. Results Compared with those of the control group, the preference index of novel object recognition test at one hour（0. 53 ±0. 09）and 24 hour（0. 51 ±0. 12）and spontaneous alternation response rate of Y maze test （0. 52% ±0. 09% ） decreased significantly for the mice in the model group （ P 〈 0. 01 ）. Compared with those of the model group, the prefer- ence index of novel object recognition test at one hour（ 0. 67 ± 0. 11 ）and 24 hour（0. 69 ± 0. 11 ） and spontaneous alterna- tion response rate of Y maze test （0. 72 % _± 0. 09 %, P 〈 0. 01 ） increased significantly for the mice in 200 mg/kg silibinin treatment group. Compared with those of the control group,the level of IL-4 decreased,but TNF-α and IL-1β increased significantly in hippocampus of the mice of the model group （ all P 〈 0. 01 ）. Compared with those of the model group, the level of IL-4 increased, but TNF-α and 1L-1β decreased in hippocampus of the mice of 200 mg/kg silibinin treatment group. Conclusion Silibinin could improve learning and memory disorder of the mice with intracerebroventricular- Aβ1-42 injection and the effects may be related to the regulation of inflammation factors in the brain.

关 键 词：水飞蓟宾 阿尔兹海默病(AD) 学习记忆障碍 炎症因子 

分 类 号：R181.24[医药卫生—流行病学]