探討δ-生育三烯醇對甲基乙二醛誘導小鼠腦神經損傷之保護效果

Study on the protective effect of δ-tocotrienol on methylglyoxal-induced cranial nerve injury in mice

張芸瑄(Zhang Yun-Xuan)

指導教授 ： 陳與國

國立屏東科技大學/農學院/食品科學系所/碩士(2019年)

https://doi.org/10.6346/NPUST201900285

摘要

甲基乙二醛 (Methylglyoxal, MG)，為糖基化終產物 (Advanced glycation end product, AGEs) 的前驅物，會在中樞神經系統中引起神經元功能障礙，其累積與多種疾病相關，例如：糖尿病及神經退化性疾病。阿茲海默症 (Alzheimer’s disease, AD) 為最常見的神經退化性疾病，主要症狀為影響患者的記憶、思維、甚至是維持日常生活的能力，而老年斑塊積累以及神經原纖維纏結為典型的病理特徵。維生素E為生育三烯醇 (Tocotrienol, T3) 及生育醇 (Tocopherol, T) 之統稱。具有抗氧化、抗老化、抗炎及神經保護等多種生理活性。文獻指出，生育三烯醇之抗氧化及抗炎等生理活性優於生育醇。本實驗選用δ-生育三烯醇作為實驗樣品，探討其在小鼠腦內對於甲基乙二醛所誘導神經損傷之保護效果，評估δ-生育三烯醇是否具有保護腦神經之潛力。實驗結果顯示，餵食δ-T3對小鼠之體重及攝食量並無顯著性影響。水迷宮試驗結果顯示，餵食δ-T3後，與負控組相比，小鼠之空間記憶學習能力有回復之趨勢。而以western blot結果顯示，餵食δ-T3後，與負控組相比，PI3K、p-Akt、p-GSK-3β及BDNF之蛋白表現量提升，且p-Tau、Aβ1-42及cleaved-caspase 3之蛋白表現量下降。總結以上結果，δ-T3具有保護MG誘導小鼠腦神經損傷之功效。

關鍵字

甲基乙二醛 ； 神經退化性疾病 ； 阿茲海默症 ； 生育三烯醇

並列摘要

Methylglyoxal (MG), a precursor of glycation end products (advanced glycation end product, AGEs), induces various stress responses in the central nervous system and causes neuronal dysfunction, and is associated with a variety of diseases, such as diabetes and neurodegenerative diseases. Alzheimer's disease (AD) is the most common neurodegenerative disease. The main symptoms are affecting the patient's memory, thinking, and even the ability to maintain daily life. Age-related plaque accumulation and neurofibrillary tangles are important typical features of Alzheimer’s disease. Vitamin E is a collective name for tocotrienol (T3) and tocopherol (T). It has many physiological activities such as anti-oxidation, anti-aging, anti-inflammatory and neuroprotection. The literature indicates that the physiological activity of T3 is better than tocopherol. In this experiment, δ-T3 was selected as an experimental sample to investigate its protective effect on nerve damage induced by methylglyoxal in mice, and to evaluate whether δ-T3 has the potential for protection of cranial nerve. The experimental results showed that the feeding of δ-tocotrienol had no significant effect on the body weight and food intake of the mice. The water maze test results showed that after feeding δ-tocotrienol, the spatial memory learning ability of mice was reverted compared with the negative control group. Western blot analysis showed that after feeding δ-T3, the protein expression of PI3K, p-Akt, p-GSK-3β and BDNF was increased compared with the negative control group, and the protein expression of p-Tau, Aβ1-42 and cleaved-caspase3 was decreased. Summarize the above results, δ-T3 has the protective effects on brain damage induced by MG in mice.

並列關鍵字

methylglyoxal ； neurodegenerative disease ； Alzheimer’s disease ； tocotrienol

參考文獻

陳原。2015。糖尿病性丙酮醛致痛機制及其清除劑鎮痛作用的研究。上海交通大學藥學院。碩士論文。

Acheson A., Conover J. C., Fandl J. P., DeChiara T. M., Russell M., Thadani A., Squinto S. P., Yancopoulos G. D., Lindsay R. M. 1995. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 374: 450-453.

Adachi H and Ishii N. 2000. Effects of tocotrienols on life span and protein carbonylation in Caenorhabditis elegans. Journals of Gerontology Series A: Biological sciences and medical sciences 55: 280-285.

Affoo R. H., Foley N., Rosenbek J., Kevin Shoemake J., Martin R. E. 2013. Swallowing dysfunction and autonomic nervous system dysfunction in Alzheimer’s disease: a scoping review of the evidence. Journal of the American geriatrics society 61: 2203-2213.

Ahmed N., Ahmed U., Thornalley P. J. 2005. Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer’s disease and link to cognitive impairment. Journal of neurochemistry 92: 255-263