纳米二氧化硅颗粒致细胞胞质分裂异常的相关机制研究

胞质分裂异常可导致细胞有丝分裂失败并引起细胞死亡或细胞的异常增殖甚至恶性转化。课题组前期研究中首次报道了纳米SiO2引起细胞有丝分裂末期胞质分裂失败并导致细胞多核这一现象，并检测到细胞分裂调控蛋白PI3K及Aurora B表达降低，但具体调控机制不清。本课题首先在体内、体外条件下检测纳米SiO2引起的毒性作用及细胞骨架损伤，并对胞质分裂过程进行实时观察，以明确纳米SiO2与胞质分裂异常的关系。同时，在体外条件下采用PI3K激活剂明确PI3K信号通路对Aurora B及胞质分裂过程的调控，采用Aurora B过表达细胞明确Aurora B对下游Centralspindlin复合体簇集、Ect2和Cep55定位以及中央纺锤体组装、收缩环形成和子细胞脱落等过程的影响，以初步阐明纳米SiO2抑制PI3K信号通路引起Aurora B功能变化在胞质分裂异常中的作用，为纳米颗粒的安全性评价提供实验依据。

Abnormal cytokinesis could result in the failure of cell mitosis, which might cause cell death or abnormal cell proliferation even malignant transformation. Silica nanoparticles led to multinucleation through abnormal cytokinesis in cultured cell line was an important phenomenon we happened to observe and reported in our previous study for the first time, while the underlying molecular mechanism was still not clear. Thus, this study will firstly detect the toxic effect and cytoskeleton damage, observe the process of mitosis real timely, and calculate the number of multinucleated cells in vivo and in vitro, to reflect the adverse effect of silica nanoparticles produced on cytokinesis. Then, some intervention measures were performed in in vitro mechanism research. PI3K activator was used to verify the regulation effect of PI3K signaling on Aurora B activity and expression, and the process of cytokinesis; Aurora B over expression cells were used to identify the influence of Aurora B on Centralspindlin complex cluster, Ect2 and Cep55 location, and the process of central spindle assembly, contractile ring formation as well as abscission. The present study will clarify the related mechanism of abnormal cytokinesis induced by silica nanoparticles and provide new perspectives for the mechanism investigation of abnormal cytokinesis induced by silica nanoparticles.