2015-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/705728摘要：奈米科技在臨床醫學和基礎生醫研究的應用突飛猛進，隨著奈米材料的持續使用，人類無可避免的會暴露於人造的奈米粒子之下。本計畫主旨在探討奈米氧化鐵對中樞發炎疾病多發性硬化症的免疫毒性，擬以實驗誘導自體免疫腦炎的小鼠疾病動物模式研究奈米鐵對中樞神經發炎之生理病理和微膠細胞的影響。奈米鐵製劑是臨床上使用的磁振造影對比劑，以靜脈注射投予，已知會被網狀內皮系統攝入。若經由鼻腔暴露，也會進入腦部，並導致微膠系胞的增生和活化。所以，吞噬細胞包含巨噬細胞和微膠細胞是體內暴露奈米鐵造影對比劑的標的細胞族群，也因此奈米鐵對免疫系統的作用受到重視。文獻中許多證據指出奈米鐵具有免疫毒性，巨噬細胞和微膠細胞的功能皆會受到奈米鐵的影響。截至目前，大多數研究報告探討奈米鐵對離體細胞或未經免疫動物的作用，計畫申請人最近研究首度指出奈米鐵對卵白蛋白免疫小鼠的抗原專一性免疫反應有顯著的作用，也會影響微膠細胞表現細胞激素。雖然，已知奈米鐵會進入到中樞神經系統，但其對中樞免疫的影響仍大都未知。多發性硬化症是一種自體免疫的漸行性神經發炎疾病，自體免疫的破壞會造成神經髓鞘的喪失和發炎，微膠細胞在此免疫病理過程中扮演關鍵角色，基於微膠細胞是奈米鐵的重要標的細胞，且奈米鐵造影對比劑會被使用於診斷神經疾病之血腦障壁的完整性，本研究的主旨在探討奈米鐵對神經發炎的衝擊，將以髓鞘蛋白免疫小鼠的自體免疫腦炎疾病模式，研究奈米鐵對多發性硬化症病變過程的神經發炎和微膠細胞功能的影響。 <br> Abstract: Nanotechnology offers promising potential in both clinical application and basic biomedical research. As the utilization of nanomaterials becomes more prevalent, human exposure to man-made nanoparticles is inevitably increased. This project aims to study the potential immunotoxicity of iron oxide nanoparticles (IONP) in multiple sclerosis (MS), the most common demyelination disorder. A murine model of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein will be employed. The murine model mimics many features of the pathophysiology of MS. IONP are focused as they are used in clinical as contrasting agents to enhance magnetic resonance imaging. For this application, IONP are administered intravenously resulting in uptake by the reticulo-endothelial system. In addition, it has been reported that intranasal administration of IONP could enter the brain and cause microglial proliferation and activation in mice. Hence, phagocytic cells, including macrophages and microglia are known to expose to IONP, raising concerns regarding the impact of IONP on the immune system. Strong evidence indicates that IONP possess immunotoxic potential. The functionality of macrophages and glia has been shown to be influenced by IONP. However, the majority of the literature reports investigated the impact of IONP on phagocytes in culture or in na&iuml;ve animal not sensitized with antigens. Recently, the applicant reported that IONP modulated antigen-specific immune responses in ovalbumin-sensitized mice. IONP also modulated the expression of proinflammatory cytokines by activated microglial cells. Although IONP are known able to reach the central nervous system (CNS), it remains mostly unclear whether IONP affect neuroimmune. MS is a progressive neuroinflammatory disorder characterized by an aberrant autoimmunity that causes the demyelination of neurons. Microglia are critically involved in the immunopathology of MS. Because superparamagnetic IONP are diagnostic agents employed for imaging the integrity of blood-brain barrier in neurological diseases, including MS. The objective of this project is to address the issue of potential impacts of nanoparticles on neuroimmune. Specifically, this project will investigate the effect of IONP on the functionality of microglia and neuroinflammation associated with multiple sclerosis (MS), the most common demyelination disease in the CNS.氧化鐵奈米粒子多發性硬化症免疫神經膠質細胞動物模式iron oxide nanoparticlemultiple sclerosisimmunemicrogliaanimal model