肺脏淋巴管的增生与重塑参与诸多肺部疾病的发生发展。我们前期研究显示纳米氧化硅肺脏/胸膜损伤和肺脏淋巴管增生与重塑密切相关，并可能通过VEGFC/D-VEGFR3-NRP2信号通路发生作用，但其详细效应与机制仍不清。本研究首先通过体外实验研究纳米氧化硅对淋巴管内皮细胞增殖、迁移、成管、分泌功能影响及VEGFC/D-VEGFR3-NRP2信号通路的效应机制；然后纳米氧化硅大鼠染毒，观察1-4周内肺脏/胸膜淋巴管增生和重塑的时间效应变化、高峰时间、部位特异性；鉴于VEGFC/D-VEGFR3-NRP2通路在淋巴管增生的重要作用，进一步使用含pSecTag-VC转基因大鼠,分别及联合阻断VEGFR3、NRP2，比较肺脏及胸膜淋巴管增生与重塑的效应和机制。该研究对认识肺脏/胸膜淋巴管增生与重塑在纳米氧化硅肺毒性中作用，对认识纳米氧化硅不同于传统二氧化硅的毒性现象与机制及其科学防护与利用具有重要意义。

Growth and remodeling of lymphatic capillaries plays a key role in the development of lung disease. Here, we will probe into the lymphatic mechanisms of lung damage caused by silica nanoparticles, which was found different to micro-silica both in patients and in rats. At first, in vitro study will be performed to detect the effect of silica nanoparticles on the morphology, proliferation, lymphangiogenesis, function of synthesis and endocrine in lymphatic endothelial cells, and the VEGFC/D-VEGFR3-NRP2 signalling. Then in vivo study will be conducted in the pSecTag-VC transgenic rats to research the growth and remodeling of pulmonary lymphatic capillaries by blocking VEGFR3, NRP2 or both. By morphological TEM observation, calculation of pleural effusion in volume, determination and analysis of VEGFC/D, VEGFR3, Prox-1 and LYVE1 in the lung/parietal pleura by methods of immunohistochemistry, western blot and RT-PCR, we will evaluate their different expressions at the levels of protein and mRNA. Also, we will evaluate the growth and remodeling of lymphatic capillaries and the role of VEGFC/D-VEGFR3-NRP2 signaling pathway in this process. This study will provide important information for our understanding the pulmonary toxicity of silica nanoparticles, the mechanisms related to lymphatic capillaries and the VEGFC/D-VEGFR3-NRP2 signaling pathway, which is of great importance for our taking effective measures to prevent the nanotoxicity and to keep the environmental health safety.