請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78366
標題: | 非侵入式物理性刺激對於神經母細胞瘤SH-SY5Y細胞受氧化壓力影響之研究 Study of the effects of non-invasive physical stimuli on human neuroblastoma SH-SY5Y cells under oxidative stress |
作者: | Yu-Yi Kuo 郭于溢 |
指導教授: | 趙治宇(Chih-Yu Chao) |
關鍵字: | 阿茲海默症,β澱粉樣蛋白,高溫療法,神經保護,發光二極體,相關色溫,電致變色材料, Alzheimer disease,beta amyloid,hyperthermia,neuroprotection,light-emitting diode,correlated-color temperature,electrochromic material, |
出版年 : | 2020 |
學位: | 博士 |
摘要: | 在現今的社會中,人的精神健康已是重大衛生議題。而由於人腦功能退化所造成的神經精神性疾病對社會的影響也愈來愈嚴重。其中,以大腦神經元漸進喪失為特徵的阿茲海默症(AD),便是當前最常見且最具破壞性的神經退化性疾病。目前已有相當多針對AD所開發的藥物,但所有現行療法中並沒有一種有效的方法可以治癒AD,至多是阻止或減輕該病惡化的進程;而這其中的原因部份可歸咎於人體血腦屏障對藥物的穿透與吸收造成的阻礙。因此,開發新且有效的替代療法是現代醫學研究至關重要的課題。在本論文中,我們採用了物理刺激作為替代藥物,並研究其使用在AD治療上的作用與效益。 首先,我們以神經母細胞瘤細胞株SH-SY5Y為模型,施以一種稱為熱循環熱療(TC-HT)的高溫療法(HT),研究其在不同氧化應激下產生的神經細胞保護效果。我們發現TC-HT的預處理可以提升SH-SY5Y細胞在過氧化氫(H2O2)引起的神經元損害下的細胞存活率;同時,其所相應的HT預處理只展現出有極低的挽救效果。而若是β澱粉樣蛋白(Aβ)對SH-SY5Y細胞的細胞毒性,TC-HT只有在與Aβ同時處理才會展現拯救的效果。這表示TC-HT對不同氧化應激的保護作用可能源於不同的細胞機制。對於H2O2,實驗結果顯示TC-HT升高了Akt蛋白的磷酸化程度,並激活了Akt / Nrf2和Akt / CREB信號傳導,從而達成保護神經的作用。另外,TC-HT也同時增進了胰島素降解酶和蛋白酶體的表現。相對地,在Aβ產生的應激下,TC-HT的保護機制不是源於磷酸化的Akt,而是由磷酸化的ERK所負責。 接著,為了研究光與神經疾病之間的關係,我們設計了一種基於電致變色材料而製成的相關色溫(CCT)調整裝置,以做到精準調節發光二極體(LED)燈泡的光色表現。實驗結果發現該裝置所造成的相關色溫變化相當靠近黑體輻射軌跡,光色變化範圍可從冷白光變到暖白光。同時,該裝置僅大幅吸收特定波長(〜480 nm)附近的大量多餘藍光,因此在CCT的調控過程中,燈泡的光通量得到了極大的保留。而不同光色對神經元細胞的影響正在進一步研究中。 物理刺激做為替代性療法可以提供良性的治療效果,並且可透過儀器調整聚焦於特定區域,以執行非侵入性的治療。這對神經退化性疾病(NDD)是一種極具潛力的治療方法,我們也希望本論文的研究結果能激發更多與物理刺激相關的AD與NDD治療研究。 To date, mental health is an important issue in either physiological or psychological aspects. Alzheimer disease (AD), featuring the progressive loss of brain neurons, is a devastating and the most common neurodegenerative disease (NDD) in current society. None of available therapies are effective to cure AD, partially due to the blood-brain barrier, and they are at most able to alleviate or halt the progress of its deterioration. Hence, it is crucial to develop alternative treatment for the relevant diseases. In this dissertation, we applied the distinct physical stimuli as the alternative agent to study the therapeutic effects on treatment of AD. In the first topic, we developed a novel strategy of hyperthermia (HT), named thermal-cycling hyperthermia (TC-HT), to treat human neuroblastoma SH-SY5Y cells under different oxidative stresses. We found that the cytotoxicity of hydrogen peroxide (H2O2) was relieved only when the SH-SY5Y cells were pretreated with TC-HT, while the corresponding HT pretreatment only rescued the cells with little effects. Meanwhile, in order to alleviate the cytotoxicity of beta amyloid (Aβ) to SH-SY5Y cells, our results showed that TC-HT should be treated together with Aβ. This result suggested that the protective effects of TC-HT against different oxidative stresses could be originated from distinct molecular mechanism. For H2O2 stress, we found that TC-HT elevated the phosphorylation of Akt protein expression, activating the Akt/Nrf2 and Akt/CREB signaling to exhibit neuroprotection. In addition, TC-HT increased the expression of IDE and proteasome proteins. By contrast, under the challenge of Aβ, the study showed that the phosphorylated ERK was responsible for the protective mechanism of TC-HT, rather than the phosphorylated Akt. In the second topic, we designed a correlated-color temperature (CCT) tuning device based on an electrochromic material to regulate the light color performance of the light-emitting diode (LED) bulb. We first showed that the CCT track of LED bulb was alongside the black-body locus, with a wide range from cold white to warm white. At the same time, the luminous flux of the bulb was greatly preserved during the modulating process of CCT, owing to the specific absorbance of excessive blue light around a certain wavelength (~480 nm). The effects of different light colors on the neuron cells were under investigation. Physical stimulation could provide benign but protective effects and focus on a specific region to perform non-invasive therapy. Therefore, with the aid of therapeutic agents, we suggest the physical stimulation can be a potential alternative remedy for AD and other NDDs. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78366 |
DOI: | 10.6342/NTU202001720 |
全文授權: | 有償授權 |
顯示於系所單位: | 物理學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
U0001-2207202010263600.pdf 目前未授權公開取用 | 11.15 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。