枯草溶菌素转化酶9（PCSK9）是一个脂质代谢调节基因，研究表明，PCSK9除调节脂质代谢之外，在As发病中还存在其他作用机制。课题组前期发现oxLDL可上调巨噬细胞PCSK9表达，PCSK9参与了oxLDL诱导的巨噬细胞炎症反应，预实验初步证实PCSK9可与TLR4相互作用。从而提出科研假说"PCSK9通过TLR4/NF-κB信号通路调控巨噬细胞炎症反应"。本项目将首先在整体动物模型和细胞模型上，采用基因转染和RNA干扰技术，以明确PCSK9表达改变对巨噬细胞炎症反应的影响。其次，运用免疫共沉淀及免疫荧光技术，进一步确定PCSK9与TLR4相互作用结合。最后，采用信号通路分级干扰策略，以阐明PCSK9对巨噬细胞炎症反应的调控作用是通过激活TLR4/NF-κB信号通路所介导。本研究可为揭示PCSK9在As发病中的作用机制提供新观点，并为As治疗提供新思路。

It is well known that proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum cholesterol. In addition to the regulation of lipid metabolism, recent studies have suggested novel biological activities of PCSK9 which may function in atherogenesis. We previously showed PCSK9 promoted oxLDL-induced macrophage inflammatory response and the potential mechanism may be related to the interaction between PCSK9 and TLR4. Therefore, we hypothesize that PCSK9 regulates the macrophage inflammatory responses through TLR4/NF-κB signaling pathway. In this study, we will use gene transfection and RNA interference to overexpress and silence PCSK9 and observe the effect of PCSK9 on macrophage inflammatory responses. Secondly, the interaction between PCSK9 and TLR4 will be further explored using co-immunoprecipitation and immunofluorescence technique. Finally, the molecular mechanism of PCSK9-regulated macrophage inflammatory responses will be investigated by blocking TLR4/NF-κB signaling pathways. This project is expected to show novel functions of PCSK9 on As, which may provide new strategies for As prevention and treatment.