维生素E 对阿尔茨海默病模型学习记忆能力损伤的改善作用

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (1): 25-31.

维生素E 对阿尔茨海默病模型学习记忆能力损伤的改善作用

赵琳, 何苗, 金万宝, 赵海山, 姚维凡, 魏敏杰

中国医科大学药学院药理教研室, 沈阳 110001, 辽宁

收稿日期:2008-04-25 修回日期:2008-09-12 出版日期:2009-01-26 发布日期:2020-10-27

Vitamin E administration improves learning and memory deficits in modeling Alzheimer' s disease

ZHAO Lin, HE Miao, JIN Wan-bao, ZHAO Hai-shan, YAO Wei-fan, WEIMin-jie

Department of Pharmacology, Pharmaceutical College of China Medical University, Shenyang 110001, Liaoning, China

Received:2008-04-25 Revised:2008-09-12 Online:2009-01-26 Published:2020-10-27
Contact: WEI Min-jie, female, professor, engaged in molecular pharmacology. Tel:024-23256666-5318 E-mail: mjwei@mail.cmu.edu.cn
About author:ZHAO Lin, female, Ph.D, engaged in molecular pharmacology.Tel:13898189120 E-mail:zl-summer@hotmail.com

摘要/Abstract

摘要： 目的: 观察维生素E 对阿尔茨海默病(AD)模型小鼠学习记忆能力的改善作用及其机制。方法: 采用D-gal 与NaNO2 联合腹腔注射方法建立AD 模型小鼠, 在造模同时及模型建立后两个时间点灌胃给予维生素E(28, 280 IU/kg) 观察疗效, 实验结束后水迷宫检测各组小鼠的逃避潜伏期的变化, 化学比色法检测脑组织AChE 、SOD 活性、MDA含量;免疫组织化学方法检测大脑皮层Aβ 、NF-B表达的变化。结果: 造模同时给予维生素E 可使D-gal 与NaNO2 联合诱导的AD 模型鼠的逃避潜伏期缩短[第1 天F(3, 56)=6.959;第2 天F(3,56)=6.689;第3 天F(3, 56)=17.379;第4 天F(3, 56)=13.391;P<0.05], AChE 活性降低[F(3, 28)=29.431, P<0.05], SOD 活性提高[F(3,28)=7.372, P<0.05], MDA 含量降低[F(3, 28)=11.235, P<0.05];同时可明显降低AD 模型鼠脑组织中Aβ 、NF-κB 的表达(P<0.05) 。模型建立后给予维生素E 未发现上述变化。结论: 维生素E 可预防化学诱导的AD 模型小鼠学习记忆能力损伤, 可能机制与提高SOD 活性、降低MDA含量、降低AChE 活性、降低脑组织中Aβ 、NF-κB 的表达等相关。

关键词: 阿尔茨海默病, 维生素E, 学习记忆损伤, 小鼠

Abstract: AIM: To investigate the protective effects of Vitamin E on learning and memory in a mouse model of Alzheimer' s disease (AD) and the mechanisms.METHODS: Mice were intragastric administrated with D-galactose (D-gal ) and sodium nitrite (NaNO2 ) or vehicle, and divided into two main groups which received Vitamin E (28 and 280 IU kg) at two different time points:either at the same time of administration, or 2 h after D-gal and NaNO2 dosing.After that, animals were trained and tested learning and memory abilities using the SMG-2 water maze.The changes of AChE and nuclear factor (NF)-κB were detected to explore the mechanism of Vitamin E' s protective effects on learning and memory deficits.RESULTS: Mice administrated with Vitamin E at the same time of D-gal and NaNO2 dosing showed a significant decrease in escape latency[F(3, 56)=6.959 on day 1;F (3, 56)=6.689 on day 2;F (3, 56)= 17.379 on day 3;F(3, 56)=13.391 on day 4;P<0.05], accompanied with significant reduction of MDA[F(3, 28)=11.235, P<0.05] and AChE activity[F(3, 28)=29.431, P<0.05], increase of SOD activity [F(3, 28)=7.372, P<0.05].Vitamin E also decreased Aβ and NF-κB expressions in the cerebral cortex of AD mice model (P<0.05).However, mice receiving Vitamin E 2 h after D-gal and NaNO₂ dosing can not reverse the learning and memory deficits.CONCLUSION: Preventive administration of Vitamin E could remarkably prevent the learning and memory impairment, the machnism may be to increase the activity of SOD, reduce the activity of AChE, the levels of MDA and the expressions of Aβ and NF-κB in the brain.

Key words: Alzheimer' s disease, Vitamin E, learningand memory deficits, mice

中图分类号:

:R741.05

赵琳, 何苗, 金万宝, 赵海山, 姚维凡, 魏敏杰. 维生素E 对阿尔茨海默病模型学习记忆能力损伤的改善作用[J]. 中国临床药理学与治疗学, 2009, 14(1): 25-31.

ZHAO Lin, HE Miao, JIN Wan-bao, ZHAO Hai-shan, YAO Wei-fan, WEIMin-jie. Vitamin E administration improves learning and memory deficits in modeling Alzheimer' s disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 25-31.

参考文献

[1] Nunomura A, Perry G, Aliev G, et al. Oxidative damage is the earliest event in Alzheimer disease[J]. J Neuropathol Exp Neurol, 2001, 60(8):759-767.
[2] Sung S, Yayo Y, Yang H, et al. Early Vitamin E supplementation in young but no aged mice reduces Aβ levels and amyloid deposition in a transgenic model of Alzheimer' s disease[J]. FASEB J, 2004, 18(2):323-325.
[3] Sommer C, Schomacher M, Berger C, et al. Neuroprotective cannabinoid receptor antagonist SR141716A prevents downregulation of excitotoxic NMDA receptors in the ischemic penumbra[J]. Stroke, 2006, 112(3):277-286.
[4] Zhang D, Liu GT, Shi JG, et al. Effects of Coeloglossum .viride var.bracteatum extract on memory deficits and pathological changes in senescent mice[J]. Basic Clin Pharmacol Toxicol, 2006, 98(1):55-60.
[5] Conte V, Uryu K, Fujimoto S, et al. Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury[J]. J Neurochem, 2004, 90(3):758-764.
[6] Drake J, Link CD, Butterfield DA.Oxidative stress precedes fibrillar deposition of Alzheimer' s disease amyloid beta-peptide (1-42) in a transgenic Caenorhabditis elegans model[J]. Neurobiol Aging, 2003, 24(3):415-420.
[7] Cui X, Zuo P, Zhang Q, et al. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice:protective effects of R-alpha-lipoic acid[J]. J Neurosci Res, 2006, 84(3):647-654.
[8] Bard F, Barbour R, Cannon C, et al. Epitope and isotype specificities of antibodies to beta-amyloid peptide for protectionagainst Alzheimer' s disease-like neuropathology[J]. Proc Natl Acad Sci USA, 2003, 100(4):2023-2028.
[9] Masliah E, Hansen L, Adame A, et al. Abeta vaccination effects on plaque pathology in theabsence of encephalitis in Alzheimer disease[J]. Neurology, 2005, 64(1):129-131.
[10] Atack JR, Perry EK, Bonham JR, et al. Molecular forms of acetylcholinesterasein senile dementia of Alzheimer' s type:selective loss of the intermediate (10S) form[J]. Neurosci Lett, 1983, 40(2):199-204.
[11] Ulrich J, Meier-Ruge W, Probst A, et al. Senile plaques:staining for acetylcholinesterase and A4 protein: acomparative study in the hippocampus and entorhinal cortex[J]. Acta Neuropathol, 1990, 80(6):624-628.
[12] Melo JB, Agostinho P, Oliveira CR.Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amy loid beta-peptide[J]. Neurosci Res,2003, 45(1):117-127.
[13] Yoshiyama Y, Arai K, Hattori T.Enhanced expression of I-kappaB with neurofibrillary pathology in Alzheimer' s disease[J]. Neuroreport, 2001, 12(12):2641-2645.
[14] Paris D, Patel N, Quadros A, et al. Inhibition of Abeta production by NF-kappaB inhibitors[J]. Neurosci Lett,2007, 415(1):11-16.

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