氧化鋅奈米微粒實驗動物攝取後體內分佈特性探討

Abstract

奈米等級之氧化鋅在多方面展現出特殊功能，已被應用於化工、光電、生醫等領域。然而有研究指出，奈米微粒進入生物體後會引起發炎、血栓形成等不良健康效應，並有透過循環系統再分佈至體內各器官、組織之虞。本研究之目的即在於了解實驗動物暴露於氧化鋅奈米微粒之後的體內分佈特性，並期望以此作為後續相關健康危害研究的基礎。 本研究分為暴露特性及動力學特性兩部份。第一部份採用八週大之Sprague-Dawley雄鼠，以全身暴露的方式分別使其暴露於粒徑大小為30 nm級及250 nm級之氧化鋅微粒下，並設定5小時及10小時兩個不同的暴露時間，於暴露結束後24小時進行犧牲。第二部份則使實驗動物暴露30 nm級之氧化鋅微粒10小時，於暴露前、暴露結束後2小時、4小時、8小時、16小時及24小時數個觀察期程分別進行犧牲，並於同樣的觀察期程另以相同一組實驗動物進行尾部採血。將取得之腦、心、肺、肝、腎等器官及血漿、血清、全血等組織，經微波消化後以感應耦合電漿質譜儀定量分析鋅濃度。 第一部份結果顯示，隨著微粒特性與暴露時間的不同，實驗動物的肝、血漿中之鋅濃度呈現明顯的劑量反應關係，肺、腎中之鋅濃度變化較不明顯，而腦、血清中之鋅濃度則不受暴露條件影響，幾乎沒有變化。第二部份結果顯示，實驗動物暴露30 nm級氧化鋅微粒10小時後，在24小時的觀察期程內，只有肝之鋅濃度在暴露結束後2小時，心之鋅濃度在暴露結束後4小時，全血之鋅濃度在暴露結束後8小時分別略微升高，隨即下降趨於穩定，其餘器官之鋅濃度則無明顯變化。 本研究之結果可供初步判斷實驗動物暴露氧化鋅奈米微粒後其體內鋅濃度的分佈情況，後續研究結果若與PBPK model結合，將可進一步探討氧化鋅奈米微粒暴露後在體內的分佈狀況，並進行相關之健康風險評估。

Nano-sized zinc oxide shows advantages in many ways and has been applied in chemical engineering, optoelectronics, biomedicine and so forth. However, some toxicological studies showed that nano particles may cause adverse health effect such as inflammation, thrombosis, etc. In addition, nano particles could be redistributed to or accumulate in the secondary organs or tissues from the deposition site by circulation. The objective of this pilot study is to explore the zinc distribution characteristics in rats after exposing to nano-sized zinc oxide. This study included two parts: exposure effects and kinetics. In the first part, 8-week-old healthy male Sprague-Dawley (SD) rats were exposed to 30 nm and 250 nm zinc oxide for 5 and 10 hrs, respectively, in a whole body exposure chamber and then sacrificed at 24 hours post-exposure. In the second part, batches of SD rats were exposed to 30 nm zinc oxide for 10 hours. As the non-exposed control batch were sacrificed without nano-sized zinc oxide exposure, the other exposed batches were sacrificed at 2, 4, 8, 16, 24 hours post-exposure. Samples of brain, lung, heart, liver, kidney, plasma, serum and whole blood were collected and digested for zinc analysis by inductively coupled plasma-mass spectrometer (ICP-MS). In the first part, there were significant dose-response relationships for zinc concentration in liver and plasma samples, while such relationships were weak in lung and kidney samples. In contrast, zinc concentrations in brain and serum samples were almost independent of the exposure conditions. In the second part, the zinc levels in liver at 2 hours post-exposure, in heart at 4 hours post-exposure and in whole blood at 8 hours post-exposure rose up slightly and then descended to the ground level, whereas the zinc level in other organs had no obvious fluctuation during the 24 hours post-exposure period. The results of this study provided some information regarding the zinc distribution pattern in rats after exposing to nano-sized zinc oxide particles. Combined with physiologically based pharmacokinetic model (PBPK model), the continued research following this pilot study can be used to explore the redistribution profile of zinc in animal model after exposing to nano-sized zinc oxide and perform the health risk assessment for nano-sized zinc oxide.