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標題: | 短期暴露於全氟癸酸對雄性Sprague-Dawley大鼠的Ppara基因表達和相關健康影響 Ppara Gene Expression and Related Health Effects of Short-Term Exposure to Perfluorodecanoic Acid in Male Sprague–Dawley Rats |
作者: | Yu-Ping Fang 方鈺萍 |
指導教授: | 劉貞佑(Chen-Yu Liu) 劉貞佑(Chen-Yu Liu | chenyuliu@ntu.edu.tw | ), |
關鍵字: | 全氟/多氟烷基化合物(PFASs),全氟癸酸(PFDA),Ppara,基因表現,管灌餵食, PFASs,PFDA,Ppara,Gene expression,Oral gavage, |
出版年 : | 2022 |
學位: | 碩士 |
摘要: | 背景 全氟癸酸是全氟碳化合物家族成員之一,其為10 個碳的長碳鍊結構,由碳氟鍵結與羧基組成,兩端分別為疏水與親水端,碳氟鍵是強化學鍵,不易被酸鹼分解且耐油耐熱,使其長時間存於環境,為持久性汙染物質。因特殊的化學特性,全氟癸酸常用在食品包材、鐵氟龍、消防泡沫等等。隨著其他全氟碳化合物被禁用與限用後,全氟癸酸的使用量遞增,在不同國家皆有觀察到其在人體血液含量增加的趨勢,又因為10個碳,導致消除速率較慢,血液半衰期長達12年。一項關於台灣食物偵測全氟碳化合物的研究,全氟癸酸在所有食品中檢出量為第一或第二高,使我們須重視全氟癸酸並探討相關健康效應。 過氧化物?體增殖物活化受體α (peroxisome proliferator-activated receptor α, Ppara)是核受體,會與配體結合,進行轉錄作用,與細胞生長、發育、調控脂質代謝有關。其配體為脂肪酸,由於全氟癸酸與脂肪酸結構相似,會被誤認成配體與之結合,進而活化影響調控,造成不良健康效應,如肝腫大。 現階段全氟癸酸研究,大多使用高劑量且腹腔注射和細胞培養實驗探討急毒性效應,但人體實際暴露劑量不高,且暴露途徑為口服,為了模擬人體暴露全氟癸酸的情形,採用較低劑量且管灌餵食老鼠實驗進行研究。 研究目的 探討低劑量的全氟癸酸與過氧化物?體增殖物活化受體在SD大鼠的多重器官的基因表現關聯性。 研究方法 將五週齡大的18隻SD大鼠分成三組: 對照組、低暴露組、高暴露組,劑量分別為 0、0.5、1 mg/kg/day (全氟癸酸),連續管灌餵食21天後,取出七個器官組織: 心臟、肝臟、肺臟、胰臟、腎臟、睪丸、血液,比較各組間的重量差異並做即時聚合?連鎖反應實驗觀察Ppara基因表現量變化。 所有統計方法使用R語言軟體,體重或器官重量採用Kruskal-Wallis分析比較三組間的差異。各組器官基因表達在不同全氟癸酸暴露劑量的差異採用Kruskal-Wallis分析和Wilcoxon 排序和檢定。劑量與各器官基因表達的相關性,採用簡單線性迴歸分析檢定線性的劑量關係效應。 結果 重量: 肝臟重量在三組間有顯著差異(p < 0.05),對照組(平均值 ± 標準差= 13.47 ± 0.73)、低暴露組(15.02 ± 1.52)、高暴露組(16.78 ± 0.93)。 基因表現: 各組基因表達中,心臟在對照組與低暴露組有顯著差異(p < 0.05)。實際食入劑量與基因表達中,與對照組相比,心臟基因表達在低暴露呈正相關 (ρ = 0.6; p = 0.01)。 結論 全氟癸酸暴露會增加肝臟重量,過氧化物?體增殖物活化受體α的基因表達在心臟組織與全氟癸酸暴露量呈正相關。 Background Perfluorodecanoic acid (PFDA) is heat-resistant and not easily degraded due to its strong carbon–fluorine bonds. With its chemical stability and widespread usage, PFDA is highly persistent in the environment. In human, PFDA has a slow excretion rate and long half-life (about 12 years in average). Because of the fatty acid-like structure, PFDA exposure may induce peroxisome proliferator-activated receptor alpha (Ppara) gene expression, increase lipid storage, and cause enlarged organs and toxicity. The purpose of this study was to explore the PFDA exposure in relation to weight and Ppara gene expressions in multiple organs in male Sprague-Dawley (SD) rats. Methods Eighteen male SD rats were divided into control, low-dose (LD), and high-dose (HD) groups randomly (n = 6 for each group). Each group received PFDA doses of 0, 0.5, 1 mg/kg of body-weight/day, ptively, via oral gavage for 21 consecutive days. Seven tissues (liver, heart, kidney, lung, pancreas, testis, and blood) were collected. Ppara gene expressions were detected by quantitative real time polymerase chain reaction (qRT-PCR). All statistical analyses were conducted using R software. The weight gains or organ weights of three groups (C, LD, HD) were compared by Kruskal-Wallis test analysis. The organs’ gene expression 2-?Ct value of each group were compared by the Kruskal-Wallis test analysis and Wilcoxon rank-sum test analysis. Linear relationship between PFDA dosage and organs’ gene expression 2-?Ct value were tested by simple linear regression. Results Weight: There was a significant difference in liver weight among the three groups (p < 0.05), the control group (mean ± SD = 13.47 ± 0.73), the low exposure group (15.02 ± 1.52), and the high exposure group (16.78 ± 0.93). Gene expression: The gene expression of each group in the heart was significantly different between the control group and the low exposure group (p < 0.05). Compared to the control dosage, there are the positive correlation in the heart in low dosage (0.5 mg/kg/day *body weight) of PFDA (ρ = 0.6; p = 0.01). Conclusions PFDA exposure may increase the liver weight and induce the Ppara gene expression level in the heart. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83468 |
DOI: | 10.6342/NTU202204010 |
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顯示於系所單位: | 環境與職業健康科學研究所 |
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