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研究生: 林依欣
Lin, Yi-Hsin
論文名稱: 尿液內的鄰苯二甲酸酯類含量在動脈粥狀硬化和尿酸之間所扮演角色的研究
Phthalate levels in urine and their associations with atherosclerosis and uric acid
指導教授: 廖寶琦
Liao, Pao-Chi
學位類別: 碩士
Master
系所名稱: 醫學院 - 環境醫學研究所
Department of Environmental and Occupational Health
論文出版年: 2018
畢業學年度: 106
語文別: 英文
論文頁數: 65
中文關鍵詞: 暴露評估腎結石鄰苯二甲酸酯類代謝物動脈粥狀硬化尿酸
外文關鍵詞: exposure assessment, kidney stone, phthalate metabolites, atherosclerosis, uric acid
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  • 在近年來,鄰苯二甲酸酯類對於人體的健康成為重要的議題。人體經由使用具磷苯二甲酸的酯類的食品包裝,成為鄰苯二甲酸進入體內的主要途徑。進入體內後,由於鄰苯二甲酸酯類並非是一個穩定的化學物質,因此在體內的半衰期短,所以在24小時以內會經由體內的代謝進入尿液,進而排出體外。根據過去的研究,鄰苯二甲酸酯類會造成呼吸系統、代謝症候群,以及性荷爾蒙的影響,但是在尿液系統上的研究仍需進一步的探討。過去的研究指出,腎結石的病程是個慢性的進程,在這過程中,也會造成慢性的腎臟傷害(CKD)。除此之外,腎結石的形成也被指出與心血關疾病(CHD)具相關性。綜合上述,本研究目的欲了解在腎結石的病人中,動脈粥狀硬化指標與鄰苯二甲酸酯類代謝物的相關性,以及尿液內的尿酸成分與鄰苯二甲酸酯類代謝物的相關性。本研究總共招募213個受試者,其中有194位腎結石病人與19位健康的人。收集其尿液,並且使用on-line-SPE-UPLC-MS系統分析尿液內的11種鄰苯二甲酸酯類的代謝物。尿液內的鄰苯二甲酸酯類代謝物與動脈粥狀硬化指標的相關性統計,結果發先:MBzP ( p < 0.016), MEHP ( p < 0.040), and MINP ( p < 0.008)與頸動脈內膜中層厚度(C-IMT)有顯著的正相關。在尿酸與鄰苯二甲酸酯類的代謝物相關性研究中,將腎結石病人依尿酸的濃度(600 mg/day)分成兩個群組。統計結果顯示,在草酸鈣結石的族群中,5oxo-MEHP (Exp(B) = 0.987, p = 0.036), 5OH-MEHP (Exp(B) = 0.994, p = 0.010), 還有 sum of DEHP ( Exp(B) = 0.995, p = 0.008)和尿液內的尿酸具有顯著的相關性。綜合以上結果,腎結石病人尿液內的鄰苯二甲酸酯類代謝物濃度與動脈硬化的指標具相關性;草酸鈣結石的病人,其尿液內的尿酸與鄰苯二甲酸酯類代謝物具相關性。

    Phthalate is a big issue in human health recently. The one of known routes of exposure to phthalates is ingestion, also a major route, due to these substances were used in food packages. Phthalates are unstable chemical compounds with short half-life that exist less than 24-hrs. They are rapidly metabolized, and then eliminated into urine. According to past studies, the phthalates would cause influences on respiratory function, metabolic syndrome, and sex hormones. However, the metabolism of phthalates through urinary system, whether exposure of them causes renal injury remains further studies. Scientists already found the formation of kidney stone is a chronic disease and related to chronic kidney disease (CKD). Furthermore, kidney stone disease has been proved commonly associated with CKD and coronary heart disease (CHD). The aims of this study were to investigate (1) the relationship between the atherosclerosis-index and levels of urinary phthalate metabolites, and (2) the relationship between the levels of urinary uric acid and urinary phthalate metabolites in patients with kidney stone. A total of 213 volunteers were recruited, there were 194 patients of kidney stone disease and 19 healthy controls. The on-line-SPE-UPLC-MS system was used to analyze all of urine samples after completing method validation of 11 phthalate metabolites. There were positive correlations between carotid intima-media thickness (C-IMT) and monobenzyl phthalate (MBzP) ( p < 0.016), mono(2-ethylhexyl) phthalate (MEHP) ( p < 0.040), and mono-isononyl phthalate (MINP) ( p < 0.008). In addition, there were significantly positive correlations between carotid score and MBzP ( p < 0.002) and MEHP ( p < 0.033). The patients with kidney stone were divided into two groups by the urinary level of uric acid (600 mg/day). Significant negative correlations were found between the patients of CaOx kidney stone and mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) (Exp(B) = 0.987, p = 0.036), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) (Exp(B) = 0.994, p = 0.010), and sum of DEHP ( Exp(B) = 0.995, p = 0.008) . These results showed that (1) the levels of phthalate metabolites in the patients of kidney stone was correlate with carotid score, and (2) there was a connection between the levels of uric acid and the levels of urinary phthalate metabolites in patients with CaOx stone.

    摘要 (III) Abstract (IV) 致謝 (VI) List of tables (IX) List of figures (X) Abbreviation (XI) Chapter 1 Research background (1) 1-1 Phthalates (1) 1-1-1 Routes of exposure to phthalate (1) 1-1-2 Phthalate metabolites in human (2) 1-1-3 Phthalate exposure is one of the potential risks of kidney stone in human (6) 1-2 CKD and atherosclerosis associated with kidney stone disease (7) 1-2-1 Measuring the carotid intima-media thickness to predict the correlation between phthalate and atherosclerosis (7) 1-3 CKD and uric acid associates with kidney stone disease (8) 1-3-1 Phthalate is associated with uric acid (9) 1-4 Ultra-performance liquid chromatography- mass spectrometry (UPLC-MS) (9) 1-5 On-line solid phase extraction (on-line-SPE) (10) Chapter 2 Objectives (11) Chapter 3 Materials and methods (12) 3-1 Research scheme (12) 3-2 Research materials and methods (14) 3-2-1 Sample collection (14) 3-2-2 Urine pretreatments (14) 3-2-3 On-line SPE-UPLC-MS system (17) 3-2-4 Measurement of carotid Intima‐Media Thickness (C-IMT) (20) 3-2-5 Statistical analysis (21) Chapter 4 Results and discussion (22) 4-1 Method validation of on-line-SPE-UPLC-MS (22) 4-1-1 Linearity (22) 4-1-2 Accuracy (26) 4-1-3 Precision (28) 4-1-4 Limit of detection and quantitation (30) 4-1-5 The general population of urinary phthalate metabolite levels in this report (31) 4-2 Demographic characteristics of volunteers (32) 4-3 Urinary phthalate metabolites between control and cases (34) 4-4 Association between the atherosclerosis-related parameters and urinary phthalate metabolites (36) 4-4-1 Linear regression of C-IMT and urinary phthalate metabolites (36) 4-4-2 Association between C-IMT and urinary phthalate metabolites (39) 4-5 Relationships between urinary concentrations of phthalate metabolites and uric acid in the kidney stone patients (40) 4-5-1 Linear regression of uric acid and phthalate metabolites (40) 4-5-2 Association between uric acid and urinary phthalate metabolites (47) Chapter 5 Conclusion (50) References (52) Appendix (60)

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