以糖尿病模式探討代謝症候群影響因子對阿茲海默氏症生化指標之影響

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題名:	以糖尿病模式探討代謝症候群影響因子對阿茲海默氏症生化指標之影響 Effects of metabolic syndrome related risk factors on Alzheimer's disease biomarkers in diabetic animal model
作者:	胡雅淳;Hu, Ya-Chun
貢獻者:	營養學系碩士班
關鍵詞:	第2型糖尿病;阿茲海默氏症;類澱粉樣前驅蛋白;乙型樣澱粉蛋白-42;Type 2 diabetes;Amyloid precursor protein;β amyloid-42
日期:	2012-07-04
上傳時間:	2012-08-31 16:34:29 (UTC+8)
出版者:	中國醫藥大學
摘要:	阿茲海默氏症(Alzheimer’s Disease)是一種漸進式且不可逆的神經性退化疾病。研究顯示，80%阿茲海默氏症患者有第2型糖尿病或是有不正常的血糖值，至今已有許多研究以顱腔注射STZ來誘發動物阿茲海默氏症，但與糖尿病病理特徵不符，因此本研究將以第2型糖尿病的動物模式來探討對於阿茲海默氏症生化指標之影響。本研究將實驗動物分為五組：Normal組(WKY大鼠)；Control組(SHR大鼠)；SS組(SHR大鼠單獨注射40mg/kg STZ)；HF組(SHR大鼠高脂飲食)；DM組(SHR大鼠高脂飲食及注射40mg/kg STZ)。檢測分析血糖、血壓、三酸甘油酯、胰島素、胰島素接受器、氧化壓力和發炎反應、Choline acetyltransferase、Amyloid precursor protein(APP)及其β amyloid-42 (Aβ42)。實驗結果顯示，在注射STZ後，胰島素的變化率及血漿中APP的變化於DM組最大；此外，HF組和DM組血漿中Aβ42則隨著血漿脂質過氧化物的增加而增加，且與肝臟中脂質的堆積增加，兩者呈現顯著高度相關性(R2=0.4174，p<0.05)；在實驗動物腦部胰島素接受器活性方面，以DM組之含量為各組中最低，且腦部Aβ42的堆積顯著增加；結果顯示，單一血壓因子和氧化發炎反應在實驗過程中並非為影響APP及Aβ42變化的主要因素。結果證實，糖尿病進展可影響阿茲海默氏症相關之生化值，胰島素阻抗與延緩失智症的發生高度相關。 Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The study showed that 80% of Alzheimer's disease patients have type 2 diabetes or abnormal blood glucose levels. Many research used an Alzheimer's disease animal model for intracerebral injection of streptozotocin. However, the pathological characteristics did not completely reflect in animals with type 2 diabetes. The purpose of the study was to investigate the effects of related risk factors on Alzheimer’s disease biomarkers by using animal model of type 2 diabetes. The animals in this study were divided into five groups: Normal group(WKY rats); Control group(SHR); SS group(SHR rats, 40mg/kg STZ for short); HF group(high fat diet); DM group (high-fat diet and injection of 40mg/kg STZ). During the study period, blood glucose, blood pressure, triglycerides, insulin, insulin receptor, oxidative stress, inflammatory markers, choline acetyltransferase, amyloid precursor protein(APP) and β amyloid-42(Aβ42) were detected. After STZ injection, the largest changes of insulin and plasma APP were shown in DM group. Furthermore, a significant high correlation was also shown in hepatic triglyceride and serum Aβ42 protein level(R2 =0.4174，p<0.05)；The brain insulin receptor activity was significantly decreased and the accumulation of brain Aβ42 was significant increased in DM group. The results show that blood pressure, oxidative stress and inflammatory biomarkers were not influential factors to APP and Aβ42 during the experiment. In conclusion, diabetes progression could affect the related biochemical markers of Alzheimer's disease. Thus, insulin resistence may be highly related to Alzheimer’s disease progression.
顯示於類別:	[營養學系暨碩士班 ] 博碩士論文

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