基于“湿毒滞络”理论探讨甘露消毒汤调控SARS-CoV-2假病毒感染hACE2转基因小鼠RAS机制研究

新型冠状病毒肺炎（COVID-19）已对公共卫生构成重大威胁，中医药在防治疫情中发挥了重要作用。SARS-CoV-2通过其S蛋白与宿主细胞上的血管紧张素转化酶2（ACE2）结合入侵，引发细胞因子风暴，与肾素-血管紧张素系统（RAS）调控失衡关系密切。本病属“湿毒疫”范畴，由疫毒直中肺络，气血郁阻，痰瘀互结所致，提出“湿毒滞络与COVID-19 RAS调控轴失衡相关”假说。甘露消毒汤由经典名方化裁而成，以汤代丹，解毒除湿，宣通肺络，临床疗效确切。利用质粒构建技术模拟S蛋白，建立SARS-CoV-2假病毒感染hACE2转基因小鼠的COVID-19模型。采用iTRAQ、ELISA、qPCR等方法检测，观察RAS调控轴ACE-AngⅡ和ACE2-Ang(1-7)及相关因子动态变化，阐明“湿毒”、“肺络”现代生物指标内涵，揭示甘露消毒汤对COVID-19整合调节机制，为临床应用提供依据。

Novel coronavirus pneumonia(COVID-19) has posed a major threat to public health, and traditional Chinese medicine has played an important role in preventing and treating the epidemic. SARS-CoV-2 invades cells by binding its S protein to angiotensin-converting enzyme 2 (ACE2) on host cells, triggering cytokine storms. Imbalance of regulation of renin-angiotension system (RAS) is closely related to it. It belongs to the category of “dampness-poison epidemic disease”. It is caused by direct injury of dampness-poison epidemic disease to the lung collaterals, obstruction of qi and blood and mutual accumulation of phlegm and blood stasis. Put forward the hypothesis that “Dampness-toxin stagnating Collaterals is related to the imbalance of COVID-19 and RAS regulation axis”. The classic formula of Ganlu Xiaodu Decoction clinical efficacy is accurate. It can detoxify, dispel dampness, free lung collaterals and made into the decoction instead of pills. The plasmid construction technique is used to simulate the S protein of SARS-CoV-2 to establish the COVID-19 model of hACE2 transgenic mice infected with SARS-CoV-2 pseudovirus. Using iTRAQ, ELISA, qPCR and other detection methods, to observe the Dynamic changes of ACE-AngⅡ, ACE2-ang(1-7) and related factors in Ras regulatory axis, and To clarify the connotation of modern biological indexes of "dampness toxin" and "lung collaterals", to reveal the integrated regulation mechanism of Ganlu Xiaodu Decoction on COVID-19, to provide basis for clinical application.