2023-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/674414塑化劑為常見的塑膠添加物，因國人於生活中經常接觸含塑化劑之塑膠產品或受塑化劑污染之食品，導致暴露劑量偏高，其中DEHP為全球最常使用的塑化劑之一，且為國人最常暴露的塑化劑。即使塑化劑造成的毒性為全球重視的食品安全及健康的議題，然而長期暴露塑化劑對生理時鐘的影響及其造成健康的負面效應的所知仍有限。生理時鐘調控眾多的細胞及生理過程，因此，一旦生理時鐘被干擾或破壞，就可能造成生物體的生理系統調控失能或疾病。 本研究計畫預計以廣泛應用於生物醫學研究的秀麗隱桿線蟲(C. elegans)為模式生物探討長期暴露DEHP對生理時鐘的影響，並進一步探討其對DEHP代謝、醣類代謝、及學習記憶的影響及可能的調控機制。本研究提出三年計畫，包含以下的三個研究目標 (specific aims)：(1)探討長期暴露DEHP是否會破壞生理時鐘及其和基因變化及DEHP代謝物之關係；(2)探討長期暴露DEHP引起的生理時鐘破壞對醣類代謝的影響及其調控機制；(3)探討長期暴露DEHP引起的生理時鐘破壞對學習記憶的影響及其調控機制。 本研究成果將提供更多及詳盡的慢性暴露塑化劑健康危害資訊，將能提供政府日後制定食品容器及其製程中DEHP釋出容許量規範的參考依據，以及DEHP每人每日耐受量參考值之參考，以保障國人日常食品安全。 Plasticizer is a common additive in plastic products and Taiwanese frequently exposed to phthalate containing products in daily life Di(2-ethylhexyl)phthalate (DEHP) is one of the most widely used plasticizer in the world including Taiwan. Phthalates contamination and their toxic effects have been an emerging global “food safety” concern as well as in Taiwan, however, the toxic effects of phthalates exposure on circadian rhythm remain largely unknown. Circadian rhythm regulates many cellular and physiological processes, once it is disrupted, the dysfunction of physiological systems or even diseases may occur. Herein, we propose a three-year project and aim to investigate the toxicity of long-term exposure to DEHP on circadian rhythm using the nematode Caenorhabditis elegans (C. elegans) as a model organism. In particular, the negative impacts on glucose metabolism and learning and memory will be discussed and the underlying molecular mechanisms will be deciphered. Three specific aims are: (1) investigating whether long-term DEHP exposure disrupts circadian rhythm and its effects on transcripts and DEHP metabolism; (2) investigating DEHP-induced circadian rhythm disruption and its impacts on glucose metabolism and its underlying mechanisms; (3) investigating DEHP-induced circadian rhythm disruption and its impacts on learning and memory and its underlying mechanisms. Results from this project will advance our knowledge on potential health hazards by long-term DEHP exposure. In addition, results from this research can provide Taiwanese government to set up the regulations for phthalates levels and TDI reference values to facilitate better food safety policies.秀麗隱桿線蟲;食品安全;塑化劑;生理時鐘;C. elegans;food safety;phthalates;circadian rhythm