臺灣博碩士論文加值系統

全氟碳化合物是由不同長度的氟化長碳鏈和帶電功能基所組成，全氟化物自1950年代起就被用於商業用途，包括使用於表面活性劑、潤滑劑、紙張與織物的表層塗料、亮光劑、食物包裝與防火泡沫。在動物實驗中，全氟碳化合物與腫瘤、肝毒性、甲狀腺毒性、免疫抑制與身體發展有關。其肝臟毒性的主要機轉是經由活化過氧化物酶體增殖物激活受體α（PPAR-α），活化PPAR-α也能降低老鼠血清中的血脂肪。全氟碳化合物是否會造成人體傷害則還未有定論，且暴露後造成傷害的機轉也都還不清楚；由於全氟碳化合物在人體也可能會活化PPAR-α受體，因此人體血中全氟碳化合物的濃度可能與胰島素抗性，脂肪代謝，進而與代謝症候群的發生率有關，但之前並無相關流行病學的報告。我們最先經由美國食品營養調查(NHANES)所提供的資料進行初步分析，首次發現血中低劑量的全氟碳化物濃度與成人肝功能異常、血糖代謝、高密度脂蛋白濃度有相關，在青少年則與血糖代謝、高密度脂蛋白濃度與代謝症候群有密切相關，結果已發表於國際期刊。在我們的文獻發表後，陸續有文獻發表全氟碳化合物在人體的濃度與膽固醇與尿酸濃度有正相關，但詳細原因還不知。目前除了國人暴露於全氟碳化合物的程度還不清楚外，人體血中全氟碳化合物與甲狀腺功能，脂肪與血糖代謝的詳細機轉甚至動脈硬化之相關性尚還不清楚。為解決上述的問題，我們以之前來自台北與台中自願參與研究的高血壓青少年與年輕成人894人分析其全氟碳化合物於血液中的濃度，結果發現研究對象暴露的全氟碳化合物濃度比美國暴露量稍低，並發現全氟碳化合物其影響血糖代謝可能主要非經由活化過氧化物酶體增殖物激活受體α（PPAR-α），而是經由活化過氧化物酶體增殖物激活受體γ（PPAR-γ）進而刺激肝細胞脂締素(adiponectin)分泌增加而影響血糖的調控，此外我們也首次發現全氟碳化合物與甲狀腺功能有正相關。希望藉由本研究之結果，將有助於了解國人對暴露全氟碳化合物潛在的健康危害風險，以作為未來在環境控制及衛生管理上的依據參考。

The perfluoroalkyl chemicals are a family of perfluorinated chemicals (PFCs) that consist of a carbon backbone. PFCs have been used extensively since the 1950s in commercial applications, including as a component in surfactants, lubricants, paper and textile coatings, polishes, food packaging, and fire-retardant foams. In animal studies, exposure to PFCs are associated with adverse health effects, including tumorigenicity, thyroid toxicity, hepatotoxicity, immune suppression, and developmental toxicity.. The agonistic properties of PFCs on PPAR-α (peroxisome proliferator-activated receptors-α) are well supported and are thought to be a major mechanism leading to PFC-mediated liver damage. PFCs also produced hypolipemia in rodents. Whether PFCs are harmful to humans has remained controversial. The causal biochemical mechanisms leading to the adverse health outcomes after exposure to PFCs are largely unknown. Since activation of PPAR-α can decrease serum triglycerides, normalize low-density lipoprotein cholesterol, and increase HDL-C. We recently analyzed the data from NHANES and found PFCs were associated with abnormal liver function tests, HDL-cholesterol and glucose homeostasis in adults. In adolescents, PFCs level were associated with abnormal glucose homeostasis, HDL-cholesterol and negative associated with metabolic syndrome. These results had been published in international journals. Other reports also demonstrate PFCs were positively associated with total cholesterol and uric acid. However, the extent of PFCs exposure in Taiwan is still unknown. Moreover, the associations between PFCs concentration, thyroid function, mechanism of lipid metabolism and atherosclerosis are still unknown. To solve the above questions, we proposed studies to investigate the association between PFCs concentration and its association with health outcomes. Besides to clarify our previous studies, the goal of the present study is to know the PFCs concentration for people in Taiwan, and we also want to examine associations between PFCs and thyroid function, lipid metabolism and atherosclerosis. Thus, a total 894 subjects from in a community-based sample of adolescents and young adults was enrolled for study. The results showed the PFC exposure in our study group is lower than data from U.S. NHANES. We also found that a higher serum concentration of PFCs was associated with elevated serum adiponectin. It is possible that PFCs increase serum level of adiponectin, decrease serum insulin level by its agonist property to PPARγ instead of PPAR-α. We also conclude that a higher serum concentration of PFCs may cause serum free T4 to increase in this cohort. We hope this study to establish better understandings about PFCs exposure of general household and potential health effect in Taiwan’s population, and used it as a reference for future environmental control and health management program design for public health prevention.

中文摘要ii
英文摘要iv
1: Background 1
1.1: Introduction 1
1.1: Introduction of perfluorinated chemicals (PFCs) 1
1.1.2: The exposure and metabolism of PFCs 2
1.1.3: Toxicity of PFCs 3
1.1.3.1: Human studies: Hepatoxocity 4
1.1.3.2: Human studies: Reproductive and developmental toxicity 4
1.1.3.3: Human studies: Lipid metabolism and atherosclerosis 5
1.1.3.4: Human studies: Glucose metabolism 6
1.1.3.5: Human studies: Thyroid toxicity 7
1.2: Specific aims 9
1.3: References 11
2: Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults 19
2.1: Introduction 19
2.2: Methods 22
2.2.1: Study design and population 22
2.2.2: Potential causes of elevated liver enzymes 24
2.2.3: Assessment of liver enzyme parameters 26
2.2.4: Assessment of PFCs concentration 27
2.2.5: Statistics 28
2.3: Results 29
2.4: Discussion 38
2.5: References 43
3: Association among serum perfluoroalkyl chemicals, glucose homeostasis and metabolic syndrome in adolescents and adults 49
3.1: Introduction 49
3.2: Research design and method 51
3.2.1: Study design and population 51
3.2.2: Anthropometric and biochemical data 51
3.2.3: Definition of metabolic syndrome 53
3.2.4: Assessment of serum PFCs 53
3.2.5: Statistics 54
3.3: Results 55
3.4: Discussion 61
3.5: Conclusion 64
3.6: Study limitations 64
3.7: References 64
4.4: Association Among Serum Perfluoroalkyl Chemicals and Adiponectin in a Young Hypertension Cohort in Taiwan 70
4.1: Introduction 70
4.2: Methods 73
4.2.1: Participants and study design 73
4.2.2: Anthropometric and biochemical data 75
4.2.3 Measurement of PFCs concentration 77
4.2.4: Definition of metabolic syndrome 78
4.2.5: Statistical analysis 79
4.3: Results 81
4.4: Discussion 86
4.5: References 90
5. Associations between Low-dose Serum Perfluorinated Chemicals and Thyroid Function in a Young Hypertension Cohort in Taiwan 96
5.1: Introduction 96
5.2: Research design and methods 99
5.2.1: Participants and study design in baseline 99
5.2.2: Paticipants and study design in follow-up 100
5.2.3: Anthropometric and biochemical data 100
5.2.4: Measurement of PFCs concentration 101
5.2.5: Statistical analysis 103
5.3: Results 104
5.4: Discussion 109
5.5: References 112
6: Conclusion 116
7: Appendix 118

1.: References
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