基于调控ACE2/ACE平衡与阻断IL-6R和GM-CSFR探究麻杏石甘汤保护肺心损伤的作用机制

COVID-19因其肺心传变引起的肺心损伤，乃至多器官衰竭。目前仍未有效的药物干预措施。麻杏石甘汤具有宣肺化浊、调气通络的功效，是COVID-19防治中常用方剂。课题组综述文献发现ACE2、GM-CSF和IL-6是COVID-19肺心损伤的三个关键因子，通过分子对接提示麻杏石甘汤中小分子化合物与上述因子受体均有较好的结合效果。基于此提出：麻杏石甘汤可通过ACE2和IL6R、GM-CSFR靶点调节ACE2/ACE平衡、抑制炎症风暴保护肺心损伤。本课题在前期分子对接筛选复方化合物的基础上，通过MST实验测定化合物与相应靶蛋白的结合亲和力；通过体外肺上皮细胞和心肌细胞损伤模型进一步优化筛选针对ACE2、IL6R、GM-CSFR不同靶点小分子配伍；以最佳配伍干预肺心损伤大鼠模型，探讨其保护肺心损伤的作用及机制。以期阐明COVID-19“肺心同治”的科学内涵，也为该方保护肺心损伤应用开发提供理论基础

COVID-19 has pulmonary heart damage caused by its pulmonary heart transmission, and even multiple organ failure. There are currently no effective drug interventions. Ma Xing Shi Gan Decoction has the effects of dispelling turbid lungs, regulating Qi and clearing the collaterals, and is a commonly used prescription in the prevention and treatment of COVID-19. The research group reviewed the literature and found that ACE2, GM-CSF and IL-6 are the three key factors of COVID-19 pulmonary heart injury. The molecular docking suggests that the small molecule compounds in Maxing Shigan Decoction have good binding to the above factor receptor effect. Based on this, it is proposed that Maxing Shigan Decoction can regulate the balance of ACE2/ ACE through ACE2 and IL6R, GM-CSFR targets, and suppress the inflammatory storm to protect lung heart injury. Based on the preliminary molecular docking screening of compound compounds, this subject determined the binding affinity of the compound to the corresponding target protein through MST experiments, and further optimized screening of different targets for ACE2, IL6R, GM-CSFR through in vitro lung epithelial cell and cardiomyocyte injury models compatibility of small molecules and intervene rat model of pulmonary heart injury with the best compatibility, and explore its role and mechanism in protecting lung heart injury. In order to clarify the scientific connotation of COVID-19 "Pulmonary Heart and Heart Governance", which also provide a theoretical basis for the development of the application of the protection of lung heart injury