基于RIPK1/RIPK3信号探讨金欣口服液调控上皮细胞程序性坏死治疗RSV肺炎机理

呼吸道合胞病毒（RSV）肺炎是小儿最常见病毒性肺炎，严重威胁儿童健康。免疫细胞过度激活导致炎症损伤靶细胞是病毒性肺炎重要病理机制。课题组前期研究焦点均在调节免疫细胞免疫信号过度活化上，而感染的靶细胞-肺上皮细胞直接保护修复也非常关键。最新研究显示，受体相互作用蛋白激酶（RIPK）1/RIPK3/MLKL系统调控RSV等病毒诱导的宿主细胞程序性坏死是引起组织损伤的关键，且预实验提示金欣口服液抑制RIPK1、RIPK3过度活化。根据文献和前期研究提出科学假说：金欣口服液可直接保护靶细胞，机制可能与其干预RIPK1/RIPK3介导的细胞程序性坏死有关。本研究建立了RSV感染体内外模型，并结合现代医学研究方法，探讨金欣口服液是否有直接靶细胞保护作用及其通过RIPK1/RIPK3调节程序性坏死机制。最终揭示该方治疗小儿RSV肺炎、保护靶细胞的科学内涵，为中医药治疗病毒性肺炎提供科学依据及新思路。

Respiratory syncytial virus (RSV) pneumonia is the most commonviral pneumonia in children, which is a serious threat to children's health.What an important molecular pathological mechanism of viral pneumonia is excessive immune activation of immune cells leads to inflammation and target cell injury. The focus of our previous research is on the overactivation of immune signals regulated by drugs. However, it is also very important that infected target cells-lung epithelial cells are protected and repaired directly by drug.Recent research has provedthat the key to tissue damage is the programmed necrosis of host cells induced by RSV which is regulated by RIPK1/RIPK3/MLKL system , and our preliminary experiments suggested that Jin Xin oral liquid could inhibit the excessive activation of RIPK1 and RIPK3.According to the literature and previous studies, we put forward the scientific hypothesis that Jinxin oral liquid could directly protect the target cells, by which mechanisms probably related to its intervention in RIPK1/RIPK3-mediated programmed necrosis of cells. In this study, we aim to explore whether Jinxin oral liquid has direct target cell protection and the mechanism of regulating programmed necrosis through RIPK1/RIPK3 using the in vitro and in vivo models of RSV infection and combining with modern medical research methods. Finally, it will reveal the internal mechanism of the prescription in the treatment of RSV pneumonia in children and the protection of target cells, and provides scientific basis and new ideas for the treatment of viral pneumonia with traditional Chinese medicine.