陶斯松、益達胺及賽滅寧之個體暴露劑量對人體代謝影響之評估與細胞模式驗證

Effect of the individual exposure to chlorpyrifos imidacloprid and cypermethrin on human metabolism and the verification in cell models

陳柏諺(Po-Yen Chen)

指導教授 ： 謝淑貞

共同指導教授 ： 呂瑾立(Chin-li Lu)

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2021年)

https://doi.org/10.6342/NTU202103124

摘要

隨著社會的進步，農藥的危害也日漸受到重視。台灣農藥使用量高，其中以殺蟲劑的佔比最大，因此本研究以殺蟲劑為標的研究其危害。目前已知各類殺蟲劑會造成肝毒性，影響代謝功能，影響腦部分神經，損害生殖系統和影響生物體活動等等，但先前研究使用之劑量均較高，並非日常可能接觸到之曝露量。為了更了解實際曝露對於人體影響，本研究利用台灣膳食暴露評估模型(TEDDM)結合國民營養健康狀況變遷調查(Nutrition And Health Survey in Taiwan, NAHSIT)中24小時飲食回顧和台灣總膳食調查計畫(Total Diet Survey, TDS)中農藥殘留結果推估陶斯松，益達胺和賽滅寧個人每日平均曝露量，並進一步分析曝露量與國民營養健康狀況變遷調查中生化指標相關性(n=1294)。在單變項回歸分析顯示許多出不同族群暴露量與生化指標具相關性，再經過考慮貢獻因子之多變項回歸後發現在老年族群中陶斯松與血三酸甘油脂有正相關性(n = 155, B = 0.03, p value = 0.035)，進一步發現老年族群中女性有正相關性(n = 155, B = 0.03, p value = 0.035)男性則無，另代謝症候族群中益達胺暴露量和低密度膽固醇有正相關性(n = 241, B = 0.02, p value = 0.041)。在考慮貢獻因子羅吉斯回歸中發現陶斯松老年Q4曝露族群會提升代謝症候群盛行率(OR: 2.413, 95% CI: 1.142 to 5.099, p value = 0.021)，進一步發現僅女性(OR: 2.906, 95% CI: 1.058 to 7.980, p value = 0.038)有此結果而男性則無，而在益達胺的部分則發現在Q2、Q3和Q4曝露量會提高女性血糖提高的盛行率(Q2之OR: 2.461, 95% CI: 1.144 to 5.294, p value = 0.021 ; Q3之OR: 2.531, 95% CI: 1.231 to 5.203, p value = 0.012 ; Q4之OR: 2.711 , 95% CI: 1.207 to 6.091, p value = 0.016)。後續進行細胞實驗欲進一步了解低劑量陶斯松對於脂肪代謝情況，使用FL83B肝細胞添加Oleic Acid的模式來分析陶斯松對於油酯累積影響，並且使用3T3-L1前脂肪細胞來研究陶斯松對於脂質細胞分化和油脂累積的影響，結果顯示接近人體暴露劑量的處理下對上述兩種細胞的脂質堆無顯著影響，推測可能因為農藥對於生物體影響難以單用細胞模式評估，未來當以多細胞的培養方式或是動物實驗來釐清陶斯松對生物體脂質代謝可能的影響。

關鍵字

陶斯松 ； 益達胺 ； 賽滅寧 ； 殺蟲劑 ； 脂肪代謝

並列摘要

The use of pesticides has always been high in Taiwan, and as society progresses, more attention is being paid to the potential hazards concerning pesticide usage. This study will focus on investigating the harmful effects of insecticides, which are heavily used in Taiwan. Previous studies have reported abnormalities of various biological processes in the body associated with the use of pesticides, including liver toxicity, metabolic dysfunction, and damage to the brain’s neural pathway and the reproductive system. However, the doses used in these studies were relatively high and unlikely to be exposed to on a regular basis. In order to better understand the impact of daily insecticide exposure on the human body, this study used Taiwan Dietary Exposure Evaluation Model (TDEEM) combined with the 24-hour dietary recall data from the Nutrition and Health Survey in Taiwan (NAHSIT) and the insecticide residues in foods reported in Taiwan Total Diet Survey (TDS) to estimate the individual daily intake of three insecticides, chlorpyrifos (CPF), imidacloprid (IMI) and cypermethrin (CYP). We also analyzed the correlation between insecticide The use of pesticides has always been high in Taiwan, and as society progresses, more attention is being paid to the potential hazards concerning pesticide usage. This study will focus on investigating the harmful effects of insecticides, which are heavily used in Taiwan. Previous studies have reported abnormalities of various biological processes in the body associated with the use of pesticides, including liver toxicity, metabolic dysfunction, and damage to the brain’s neural pathway and the reproductive system. However, the doses used in these studies were relatively high and unlikely to be exposed to on a regular basis. In order to better understand the impact of daily insecticide exposure on the human body, this study used Taiwan Dietary Exposure Evaluation Model (TDEEM) combined with the 24-hour dietary recall data from the Nutrition and Health Survey in Taiwan (NAHSIT) and the insecticide residues in foods reported in Taiwan Total Diet Survey (TDS) to estimate the individual daily intake of three insecticides, chlorpyrifos (CPF), imidacloprid (IMI) and cypermethrin (CYP). We also analyzed the correlation between insecticide exposure and biochemical indicators available from NAHSIT. Univariate regression and multivariate regression analyses showed that individual daily intake of CPF was significantly and positively correlated with blood triglycerides in the elderly (n = 330, B = 0.02, p value =0.039). Furthermore, elderly females, involve in the significantly and positively correlation but males did not (female n = 155, B = 0.03, p value=0.035). Besides, individual daily intake of IMI was significantly and positively correlated with blood low-density lipoprotein cholesterol in the population with metabolic syndrome (n = 241, B = 0.02, p value = 0.041). Logistic regression shows CPF increase metabolic syndrome odds ratio in the elderly group (OR: 2.413, 95% CI: 1.142 to 5.099, p value = 0.021), again, female but not males contribute to the difference (female OR: 2.906, 95% CI: 1.058 to 7.980, p value = 0.038). Besides, IMI increases the hyperglycemia odds ratio in Q2, Q3 and Q4 females groups (Q2 OR: 2.461, 95% CI: 1.144 to 5.294, p value = 0.021 ; Q3 OR: 2.531, 95% CI: 1.231 to 5.203, p value = 0.012 ; Q4 OR: 2.711 , 95% CI: 1.207 to 6.091, p value = 0.016). To investigate the effects of CPF on lipid metabolism, we further treated FL83B hepatocytes, which accumulate lipid upon oleic acid incubation and adipocytes obtained from the differentiation of 3T3-L1 preadipocytes with the insecticides at doses that reflected the mean individual daily intake. However, the results showed that the doses applied did not cause any significant changes on lipid metabolism. It probably results from that CPF causes systemic effects on the whole body and not just one or two organs, suggesting that cell models that simulate a single cell environment is not proper to confirm the events from the interaction of different organs.

並列關鍵字

chlorpyrifos ； imidacloprid ； cypermethrin ； insecticide ； lipid metabolism

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