从JAK1/2-STAT1通路介导的“细胞因子风暴”研究流行性感冒“肺脑传变”分子机制与麻杏石甘汤干预作用

“流感相关性脑病”（流感病毒呼吸系统急性感染过程中伴中枢神经功能障碍之临床综合征）是流感危重并发症之一。尽管其危害已被高度重视，但其“肺脑传变”分子机制尚无报道。本项目在“流感肺炎小鼠模型伴有脑组织病理损伤”研究基础上，先用流感肺炎模型，从呼吸功能和神经功能、肺组织和脑组织病理变化及病毒载量研究其“肺脑传变”病理机制与麻杏石甘汤（流感防治中倍受重视）干预效应；再用流感病毒刺激共培养体系中的肺巨噬细胞、脑巨噬细胞，以实时荧光定量PCR、Western blot、激光共聚焦显微技术等，从基因与蛋白表达水平、活化与功能状况研究介导“细胞因子风暴”的JAK1/2-STAT1通路主要“元件”的变化与麻杏石甘汤调控作用；最后用流感肺炎模型，从通路改变与呼吸功能、神经功能、肺组织和脑组织病理损伤的相关性研究其“肺脑传变”分子机制与麻杏石甘汤调控机制，注释流感“肺脑传变”科学内涵，拓展麻杏石甘汤临床应用。

‘Influenza associated encephalopathy’(A clinical syndrome with a series of central nervous dysfunction in the acute phase of influenza) is a critical complication of influenza infection.Although its harm has attracted wide attention,the molecular mechanism of‘pathogenesis transmission between the lung and brain’has not been reported. Based on the research of‘influenza pneumonia mouse model with brain pathological damage’,in this project,We firstly analyzed the changes in respiratory and neurological functions,the pathological changes of lung and brain tissue,and the variation of viral load to explore the Pathological mechanism of‘pathogenesis transmission between the lung and brain’and the intervention effect of Maxing Shigan Decoction(A Classical Chinese herbal formula in the prevention and treatment of influenza). Secondly,influenza virus was used to stimulate pulmonary macrophages and brain macrophages in the coculture system,and the changes of key elements of JAK1/2-STAT1 Signaling pathway-mediated‘cytokine storm’and the regulatory effect of Maxingshigan Decoction were studied by real-time fluorescence quantitative PCR, Western blot and laser confocal microscopy. Finally, we use the influenza pneumonia mouse model to study the molecular mechanism of‘pathogenesis transmission between the lung and brain’and the regulatory mechanism of Maxingshigan Decoction from the correlation between the change of signal pathway and the pathological damage of respiratory function,nerve function,lung tissue and brain tissue.It better annotates the scientific connotation of‘pathogenesis transmission between the lung and brain’of influenza,and expand the clinical application scope of Maxingshigan Decoction.