纳米银对胆道闭锁小鼠NK细胞数量及活性的影响及其机制研究

研究表明胆道闭锁(biliary atresia，BA)与病毒感染及胆道炎症反应密切相关，其中NK细胞是BA小鼠病程早期最重要的免疫细胞。纳米银(AgNp) 具有抗病毒和抗炎作用，我们最近研究表明：AgNp可显著提高轮状病毒诱导的BA小鼠的存活率，减低黄疸，提升体重；预实验显示：AgNp对轮状病毒并未有显著的抑制作用，但可降低BA小鼠肝内炎症程度，并显著抑制NK细胞数量。AgNp通过何种机制抑制NK细胞？我们的前期蛋白质组学数据表明AgNp可激活间充质干细胞的TGF-β信号通路，而TGF-β对NK细胞具有抑制作用，提示AgNp可能通过上调TGF-β抑制BA中NK细胞的数量及活性。本项目拟探讨①AgNp是否通过抑制NK细胞治疗BA小鼠；②AgNp通过何种机制抑制BA小鼠NK细胞。旨在阐明AgNp对BA小鼠NK细胞的影响及其分子和细胞学机制，为研发治疗BA的有效药物提供新的思路和理论基础。

Biliary atresia (BA) is closely related to viral infection and biliary inflammation, and NK cells are the most important immune cells in the early disease phase of BA mouse. Silver nanoparticle (AgNp) have the properties of antiviral and anti-inflammatory. Our preliminary experiment results showed that AgNp could significantly improve the survival rate of mice which induced by rotavirus, recover skin jaundice, lift weight. Further analysis showed that AgNp could reduce its liver inflammation, significantly inhibit the number of NK cells without virus inhibition. What’s the mechanism for AgNp to inhibit the NK cells in BA mice? Our preliminary proteomics results showed that AgNp could activate TGF-β signaling pathway in human mesenchymal stem cells. Hence, we hypothesized that AgNp may inhibit the NK cells mediated biliary inflammation in BA mice by up-regulating the expression of TGF-β. This study intends to investigate ①whether AgNp ameliorated BA syndrome in BA mice is through the inhibition of NK cells; ② the mechanism of inhibition effect in NK cell activation by AgNp treatment. To elucidate the molecular and cellular mechanism of AgNp in the treatment of BA mice’s NK cells. This project will laid a theoretical and experimental basis for AgNps developed into an effective drug in the treatment of BA.