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维生素E、乙酰-L-肉碱和α-硫辛酸对大鼠阿尔茨海默病模型中新潜在生物标志物的调节作用

Modulatory effects of vitamin E, acetyl-L-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer's disease in rat model.

作者信息

Ahmed Hanaa H

机构信息

Hormones Department, National Research Centre, Dokki, Cairo, Egypt.

出版信息

Exp Toxicol Pathol. 2012 Sep;64(6):549-56. doi: 10.1016/j.etp.2010.11.012. Epub 2010 Dec 23.

Abstract

Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder associated with aging. This study aimed to explore new markers for AD as total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); to determine the modulatory effects of vitamin E (VE), acetyl-L-carnitine (ALC) and α-lipoic acid (LA) on the investigated parameters and to evaluate the possible therapeutic role of these nutraceutical in AD-induced in rats. Our results revealed that brain acetylcholine esterase (AChE) activity and tHcy levels were significantly increased in AD model. Folic acid, vitamin B(12) levels and Na(+)/K(+) ATPase activity were markedly reduced. Plasma insulin and IGF-1 levels were noticeably decreased but plasma TNF-α and IL-1β concentrations were significantly increased, confirming that abnormal inflammatory response is associated with AD. Treatment by VE, ALC and LA restored the above mentioned parameters to about normal levels comparable to those of donepezil, indicating that tHcy, insulin, IGF-1, IL-1β and TNF-α may be considered as new biomarkers for AD. The study points to the potential restoring effects of VE, ALC and LA in AD model. Our study provides evidence for the importance of dietary supplementation in delaying the progression of age-related neurodegenerative diseases.

摘要

阿尔茨海默病(AD)是与衰老相关的最常见的慢性神经退行性疾病。本研究旨在探索AD的新标志物,如总同型半胱氨酸(tHcy)、胰岛素、胰岛素样生长因子-1(IGF-1)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α);确定维生素E(VE)、乙酰-L-肉碱(ALC)和α-硫辛酸(LA)对所研究参数的调节作用,并评估这些营养保健品在大鼠AD模型中的可能治疗作用。我们的结果显示,AD模型中脑乙酰胆碱酯酶(AChE)活性和tHcy水平显著升高。叶酸、维生素B12水平和Na+/K+ATP酶活性明显降低。血浆胰岛素和IGF-1水平显著下降,但血浆TNF-α和IL-1β浓度显著升高,证实异常炎症反应与AD相关。VE、ALC和LA治疗可将上述参数恢复至与多奈哌齐相当的正常水平,表明tHcy、胰岛素、IGF-1、IL-1β和TNF-α可被视为AD的新生物标志物。该研究指出了VE、ALC和LA在AD模型中的潜在恢复作用。我们的研究为膳食补充剂在延缓与年龄相关的神经退行性疾病进展中的重要性提供了证据。

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