母體暴露鄰苯二甲酸二 (2-乙基己基) 酯對過敏性氣喘之影響

The effect of transmaternal exposure to Di-(2-ethylhexyl) phthalate on the allergic asthma

吳泰廷(Tai-Ting Wu)

指導教授 ： 孫昭玲

高雄醫學大學/醫學院/醫學研究所/博士(2013年)

https://doi.org/10.6832/KMU.2013.00120

摘要

前言：鄰苯二甲酸二 (2-已基己基) 酯 (DEHP) 之廣泛使用，使其成為無所不在的環境干擾化學物質，目前的研究指出，母體暴露DEHP會影響子代生殖系統的發育與調控，但對於過敏性疾病發展的影響目前並不清楚。
實驗方法：建立模擬人類暴露之氣喘動物模式，依照歐盟所公布DEHP的人體每日可容許攝取量 (37 μg/kg body weight/day) 做為餵食母鼠的劑量，在母鼠持續餵食10天後開始交配，且其間持續管餵不間斷，其生產下的小鼠 (F1與F2子代) 利用OVA致敏化，分析在子代肺部發炎的情形與脾臟免疫細胞的比例與功能變化。
結果：母體長期暴露低劑量DEHP，會促使F1及F2子代在幼鼠時期時過敏性氣喘更為嚴重，且脾臟內cDCs與pDCs的比例與數量有明顯下降，調節性T細胞轉錄因子Foxp3平均的表現量有上升的趨勢，在成鼠時DEHP的影響會降低，這些發炎性指標皆無顯著性的變化；純化F1子代脾臟cDC11c+樹突細胞，其分泌IL-6的能力有顯著性的上升。
結論：本研究證實了母體長期暴露低劑量的DEHP會影響F1以及F2子代的過敏性發炎調控，可能與DC族群的功能變化有關。

關鍵字

鄰苯二甲酸二 (2-乙基己基) 酯

並列摘要

Background: Due to the wide use of Di-(2-ethylhexyl) phthalate (DEHP), it has become an ubiquitous environmental disrupting chemical. Previous studies demonstrated that maternal exposure to DEHP affects the development of reproductive system in their offspring; however, the effect of maternal DEHP exposure on the development of allergic disease is not clear now.
Methods: To simulate the relevant route of DEHP exposure in humans, female C57BL/6 mice were oral injected with 37 μg DEHP/kg body weight/day for 10 days before mating and throughout their pregnancy and lactation. The F1 and F1pups were immunized with OVA and lung inflammation and spleen subsets were assessed.
Results: After low-dose and long-term exposure to DEHP, both F1 and F2 neonates developed severe allergic lung inflammation than control F1 or F2 mice did, respectively. It showed eosinophil infiltrate and Th2 cytokine pattern in DEHP-exposed offspring. In addition, the number and percentage of conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) had significantly decreased. However, there was no significant methanol and DEHP effect on the adult F1and F2 offspring. Furthermore , cDCs from F1 offspring secreted more IL-6 in response to TLR-4 and TLR-9 signaling.
Conclusion: This study suggests that low-dose and chronic maternal exposure modulates the function or differentiate of cells, especially cDCs.

並列關鍵字

Di-(2-ethylhexyl) phthalate

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