紅肉李對STZ誘發之糖尿病大鼠認知功能及大腦神經退化相關蛋白質表現的影響

Effects of oriental plums on the expressions of the cognitive function- and the cerebral neurodegeneration-related proteins in STZ-induced diabetic rats

李高廷(Kao-Ting Lee)

指導教授 ： 林士祥

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2012年)

https://doi.org/10.6831/TMU.2012.00056

摘要

超過95%的阿茲海默症病人屬於偶發性阿茲海默症。過去研究指出第二型糖尿病為偶發性阿茲海默症的危險因子之一，其主要原因可能是胰島素抗性導致胰島素訊息傳遞的受損，使腦部蛋白質表現異常而造成認知功能衰退。在動物及臨床研究上，多酚類物質已被應用於預防阿茲海默症的發生，然而至今仍缺乏多酚類物質預防糖尿病引起阿茲海默症的動物研究。本實驗目的為探討富含多酚類物質的紅肉李（Prunus salicina Lindl）對第二型糖尿病大鼠認知功能及大腦神經退化之相關蛋白質表現的影響。將nicotinamide/streptozotocin誘發的第二型糖尿病大鼠介入紅肉李飲食兩個月，並對照糖尿病用藥metformin之正控制飲食。以莫氏水迷宮及被動迴避試驗評估大鼠的認知功能，並評估胰島素抗性、血清脂質過氧化程度及大腦中阿茲海默症病理蛋白質β-澱粉樣蛋白（Aβ）及磷酸化tau蛋白的表現。結果發現餵食紅肉李可顯著改善糖尿病大鼠的高血糖、胰島素抗性及空間學習能力，降低血清脂質過氧化程度、大腦皮質Aβ及磷酸化tau蛋白的表現（p < 0.05），並減少海馬迴Aβ的堆積。紅肉李可能透過降低高血糖、胰島素抗性及氧化壓力，而降低大腦中阿茲海默症病理蛋白質的表現，進而減緩糖尿病大鼠認知功能的衰退。

關鍵字

阿茲海默症 ； 糖尿病 ； 紅肉李 ； metformin ； 認知功能

並列摘要

More than 95% of Alzheimer’s disease (AD) patients are sporadic AD (sAD). It has been shown that Type 2 diabetes is one of the risk factors of sAD. The impaired insulin signaling caused by the insulin resistance, which results in abnormal protein expressions in the brain and cognitive decline. In the animal and clinical studies, polyphenols have been used to prevent the incidence of AD. However, studies related to preventing diabetes-caused AD with polyphenols are still limited. The purpose of this study was to examine the effect of the polyphenol-rich oriental plum (Prunus salicina Lindl) on the cognitive function and cerebral neurodegeneration-related protein expressions in the Type 2 diabetic rats. Nicotinamide/streptozotocin-induced diabetic rats were treated with diabetes medication, metformin, or oriental plums for 2 months. The cognitive function was assessed by Morris water maze and passive avoidance test. The insulin resistance, serum lipid peroxidation, and expressions of pathology protein of AD, beta-amyloid (Aβ) and phosphorylated tau protein were also assessed. Results showed that consuming oriental plums significantly improved the spatial learning ability, reduced the insulin resistance, lipid peroxidation, Aβ and phosphorylated tau protein expressions of cerebral cortex (p < 0.05), and decreased the Aβ deposition of hippocampus in the diabetic rats. In conclusion, consuming oriental plums ameliorated the cognitive decline and reduced the expressions of pathology protein of AD by possibly reducing the hyperglycemia, insulin resistance and oxidative stress in the diabetic rats.

並列關鍵字

Alzheimer’s disease ； diabetes ； oriental plum ； metformin ； cognitive function

參考文獻

Ghosh D, Konishi T. 2007. Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function. Asia Pac J Clin Nutr 16:200-208.

ADA. 2011. Clinical practice recommendations. Diabetes Care 34(Suppl 1):S11-S61.

Ainsworth EA, Gillespie KM. 2007. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent. Nat Protoc 2:875-877.

Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA. 2005. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8:111-120.

Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. 2004. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 61:661-666.