發(fā)布時間：2018-05-20 08:49

  本文選題：阿爾茨海默病 + SMC　； 參考：《深圳大學》2017年碩士論文

【摘要】：阿爾茨海默病(Alzheimer’s disease,AD)是一種與年齡相關的神經退行性疾病,其主要特點是記憶缺失和認知損傷。AD的病理特征主要表現(xiàn)為由Aβ沉積形成的老年斑塊和由tau蛋白過度磷酸化所形成的神經纖維纏結(NFT)。此外,線粒體動力學異常和功能障礙、自噬損傷和金屬離子內穩(wěn)態(tài)紊亂等在AD的發(fā)展過程中也起著重要的作用。生物必需微量元素硒對維持中樞神經系統(tǒng)的正常功能具有重要作用,長期缺硒會引起包括AD在內的多種腦疾病。硒甲基硒代半胱氨酸(SMC)是一種廣泛存在于植物中的天然有機硒化合物,與無機硒相比,具有毒性低,生物利用度高等特點。SMC具有明顯的抗氧化和抗腫瘤作用,但其在神經退行性疾病包括AD中的作用尚無報道。本研究中,我們采用三轉基因AD模型小鼠(3×Tg AD),通過水迷宮、曠場實驗、Western blot、ICP-MS、同步輻射X射線熒光(SR-XRF)、Gallys染色、尼氏染色和線粒體延時成像等方法,研究了SMC(3μg/m L)從2月齡開始給藥12個月對AD模型小鼠的相關病理指標的干預作用和分子機制。研究發(fā)現(xiàn):1、SMC顯著提高AD模型小鼠的空間學習能力和記憶能力,并改善AD模型鼠的焦慮情緒;2、SMC抑制AD模型小鼠腦內Aβ病理和tau病理,改善神經元活性和突觸蛋白的表達;3、SMC對AD模型小鼠腦內多種金屬離子的含量和分布異常具有一定的調節(jié)作用;4、SMC通過調控雷帕霉素靶酶(mTOR)活性促進自噬發(fā)生,進而促進自噬體生成自噬溶酶體,以清除錯誤折疊蛋白。5、SMC通過激活AKT促進線粒體的生物發(fā)生并抑制線粒體凋亡;通過調節(jié)線粒體能量代謝相關蛋白的表達糾正體內ATP產生障礙;維護線粒體分裂融合的平衡并改善線粒體在神經元軸突內的運輸障礙;保護線粒體膜電位和并抑制線粒體膜孔通道的過度開放�；赟MC對AD模型中Aβ病理和Tau病理的干預作用,對金屬離子內穩(wěn)態(tài)的調控作用,對自噬受損的改善作用,及對線粒體動力學和功能的保護作用,有望將SMC開發(fā)為一種潛在的AD干預藥物或保健品。
[Abstract]:Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main features of AD are memory loss and cognitive impairment. The pathological features of AD are mainly age-related plaques formed by A 尾 deposition and neurofibrillary tangles formed by excessive phosphorylation of tau protein. In addition, mitochondrial kinetic abnormalities and dysfunction, autophagy and metal ion homeostasis also play an important role in the development of AD. Selenium, an essential microelement, plays an important role in maintaining the normal function of the central nervous system, and chronic selenium deficiency may cause many brain diseases, including AD. Selenomethylselenocysteine (SMC) is a natural organic selenium compound widely found in plants. Compared with inorganic selenium, SMC has the characteristics of low toxicity and high bioavailability. However, its role in neurodegenerative diseases, including AD, has not been reported. In this study, we used three transgenic AD mice with 3 脳 TG adriamycin, water labyrinth, open field experiments, Western blotl ICP-MS, synchrotron radiation X ray fluorescence (SR-XRF) Gallys staining, Nissl staining and mitochondrial delay imaging, etc. The effects and molecular mechanisms of SMC(3 渭 g / mL on the pathological parameters of AD model mice were studied in 12 months from the age of 2 months. It was found that SMC significantly increased the ability of spatial learning and memory in AD model mice, and improved anxiety in AD model mice. SMC inhibited A 尾 pathology and tau pathology in brain of AD model mice. Ameliorating neuronal activity and synaptophysin expression of SMC could promote autophagy by regulating the activity of rapamycin target enzyme mTORs and regulating the abnormal contents and distribution of multiple metal ions in brain of AD model mice. In order to remove the misfolded protein. 5SMC can promote mitochondrial biogenesis and inhibit mitochondrial apoptosis by activating AKT, and correct the ATP production barrier by regulating the expression of mitochondrial energy metabolism-related proteins in vivo, and promoting the formation of autophagy lysosome in autophagy. Maintain the balance of mitochondrial fission and fusion and improve mitochondrial transport barrier in neuronal axons, protect mitochondrial membrane potential and inhibit the excessive opening of mitochondrial membrane pore channel. Based on the intervention of SMC on A 尾 pathology and Tau pathology in AD model, the regulation of metal ion homeostasis, the improvement of autophagy damage, and the protection of mitochondria dynamics and function were observed. SMC is expected to be developed as a potential AD intervention drug or health care product.
【學位授予單位】：深圳大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.16

【參考文獻】

相關期刊論文 前1條

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本文編號：1913957