隨著奈米科技的發展，奈米材料已廣泛的運用在生活之中。本研究測試及比較了七種不同細胞株，分別為肺臟、肝臟、腎臟、小腸、皮膚與免疫系統，暴露在四種不同表面修飾(如檸檬酸鈉和2-氨基乙硫醇)與大小(約20奈米及50-80奈米)的奈米銀粒子(分別為SCS、LCS、SAS與LAS)中所造成的毒性影響。為了探討詳細的細胞作用機制，我們對這些微粒所誘導的細胞自噬、細胞週期停滯與細胞凋亡間的相互關係進行研究。此外我們也以腹腔注射小鼠的模式測試奈米銀的急毒性與生物動力學影響。
實驗中我們測定了這些奈米銀的物化特性與對不同細胞株的細胞毒性。當細胞暴露不同奈米銀粒子24與48小時以後我們使用MTT/MTS分析法進行測試，分析後所得數據以樹狀分類模型(J48)進行預測模型的建構。為了探討奈米銀所誘導的細胞自噬、細胞週期停滯與細胞凋亡間的關係，我們使用Acridine orange、Propidium iodide及Annexin V-FITC/PI 染色並透過流式細胞儀分析與西方墨點法觀察蛋白表現，藉此探討奈米銀所誘導細胞產生細胞自噬、細胞週期停滯與細胞凋亡之間的關係。不同種類及濃度的奈米銀粒子以腹腔注射方式注入BALB/c小鼠體內，所有的動物在給藥後2、7或14天犧牲。分析小鼠的各項血清生化值與組織病理判斷其毒性影響，並使用Graphite Furnace Atomic Absorption (GF-AA)與Non Invasion In Vivo Imaging System (IVIS)分析其生物動力學。
根據樹狀圖模型我們排序了影響毒性的參數，依序為:奈米銀濃度(最具影響力)、暴露細胞種類(細胞敏感度由高到低依序為: IEC-6 ≧BEAS-2B ≧HEK-293 > AML12 >Clone-9 = HaCaT= THP-1)、奈米銀種類(毒性由強到弱: SCS> SAS≧LCS> LAS)。我們也證實了暴露15 μg/ml的奈米銀會誘發細胞自噬與細胞凋亡。在低濃度的奈米銀暴露中細胞週期停滯蛋白，如p27、CDK2、Cyclin A 與 Cyclin B會隨著細胞自噬的相關蛋白表現的增加而減弱。在動物實驗中，我們發現注射8 mg/kg SCS能夠誘發小鼠產生顯著的毒性，但除了胰臟外，並無發現其它器官有明顯的受損情形。
根據本篇研究結果，我們認為KDD模式能夠有效的幫助我們建構毒性分析模型。我們也發現到LCS奈米銀在不同劑量下所誘導的細胞機制不同。在動物模型中，我們證實了注射SCS能夠誘發小鼠出現顯著的毒性反應，也在胰臟中觀察到受損的現象。

In this study, the toxicological effects of four sliver nanoparticles (AgNPs) with different surface-modified and size were examined and compared by using seven different cell lines representing lung, liver, kidney, intestine, skin and the immune system, and evaluated the acute toxicity and biokinetics of intraperitoneal administered silver nanoparticles (AgNPs) in mouse model. We employing MTT/MTS test as end point assays following exposures AgNPs. Data analysis and predictive modeling of the obtained data sets was executed by employing a decision tree model. Flow cytometry and western blot was used to analyze the levels of autophagy, cell cycle arrest and apoptosis. Mice were intraperitoneal injected with different types and dosages of AgNPs and sacrificed on day 2, 7 or 14 after exposure. Toxic effects were assessed via serum biochemical parameters and histopathological observation of the mice. Biokinetics of AgNPs were determined by GF-AA and IVIS. The decision tree model yielded the following order with decrease of the ranking parameter. We demonstrate that exposure to AgNPs induced autophagy, apoptosis, cell arrest and cell senescence in AML12 cells. In vivo study showed significant toxicity in 8 mg/kg SCS treatment mouse and demonstrated damage in pancreas.

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