基于NF-κB/POU2F2-PLCβ2通路的六神丸抑制新型冠状病毒所致炎症的作用机制研究

新冠肺炎已升级为国际突发公共卫生事件，疫苗药物研发迟滞，严重危害人类健康。炎症因子风暴是导致病情恶化及致死的重要原因。中医药及早干预是我国抗疫宝贵经验。六神丸作为推荐用药，在治疗热病及其炎症疗效显著。前期研究也证实六神丸抑制新型冠状病毒的体外复制，改善病毒感染所致炎症紊乱，并发现NF-κB/POU2F2-PLCβ2通路的靶向调控或为六神丸重要作用机制。为此，拟通过生物信息学分析及双荧光素酶报告基因明确NF-κB p65、POU2F2与PLCβ2三者的转录调控；构建PLCβ2、NF-κB p65及POU2F2的干扰及过表达细胞模型，验证六神丸靶向NF-κB/POU2F2通路影响PLCβ2的转录调控而抑炎；构建SARS-CoV-2感染小鼠模型，进一步验证六神丸抑制新冠肺炎作用机制，全面阐明六神丸对病毒及其所致炎症的药理学机制，为科学诠释其“清热解毒”的治疗优势及其新药研发奠定基础研究依据。

COVID-19 has been upgraded to an international public health emergency, and the delay in vaccine and drug development has seriously endangered human health.Inflammatory factor storms are an important cause of deterioration and death.The early intervention of traditional Chinese medicine is a valuable experience in fighting the epidemic in China.Liu Shen Wan was recommended for the treatment of fever and inflammation.Previous studies have also confirmed that Liu Shen Wan inhibited the replication of novel coronavirus in vitro, improved the inflammatory disorder caused by virus infection, and found that the targeted regulation of NF-κB/POU2F2-PLCβ2 pathway may be an important mechanism of action of Liu Shen Wan.Therefore, the transcriptional regulation of NF-κB p65, POU2F2 and PLCβ2 was determined by bioinformatics analysis and the dual luciferase reporter.The interference and overexpression cell models of PLCβ2, NF-κB p65 and POU2F2 were constructed to verify that Liu Shen Wan affected the transcriptional regulation of PLCβ2 and inhibited inflammation by targeting the NF-κB/POU2F2 pathway.The mice model of SARS-CoV-2 infection was constructed to further verify the mechanism of Liu Shen Wan on inhibiting COVID-19, comprehensively elucidated the pharmacological mechanism of Liu Shen Wan on virus and its inflammation, and laied a foundation for scientific interpretation of its therapeutic advantages of "clearing heat and detoxification" and the development of new drugs.