扶正解毒法干预RORγt/Foxp3失衡对肺炎感染后免疫稳态的调控机制研究

The body's immune homeostasis after pneumonia infection, and antibiotic resistance is serious, if the control of infection improperly，even can host organism pathological damage or death. Researches have found that the destruction of the immune homeostasis after infection associated with RORγ t/Foxp3 imbalances, and patients, pathogens and drug interaction to play a therapeutic effect. Team found early pneumonia is "virtual", "because of the deficiency disease" theory is put forward, the centralizer detoxification method can regulate the body's immunity, reduce inflammation damage, improve the effect of antibiotic treatment, reduce the mortality of experimental animals in early stagle, but the specific mechanism and the target is unknown. This research intends to develop research based on regulating the immune imbalance after infection. Set up rats streptococcus pneumonia infection model by dropping inhalation from trachea, discuss drug of centralizer detoxification and its demolition of experimental animals RORγt/regulatory mechanism of Foxp3 immune imbalance by using enzyme-linked immunosorbent method and real time quantitative PCR methods. Through researching the centralizer detoxification method targets and mechanisms of immune imbalance regulation for the prevention and treatment of traditional Chinese medicine provides the reference for the basic research and clinical application of pneumonia infection and train of thought.

肺炎感染后机体免疫稳态破坏，且抗生素耐药严重，若感染控制不当可引起机体病理损伤甚至宿主死亡。感染后免疫稳态破坏与RORγt/ Foxp3失衡有关，既往研究主要针对病原体，药物与患者、病原体相互作用才能起到很好疗效。课题组前期发现肺炎初期即存在"正虚"，提出"因虚致病"理论，扶正解毒法可调节机体免疫，减轻炎症损伤，从而发挥治疗作用，具体机制不详。本项目拟基于调控感染后免疫失衡开展研究，大鼠气管内滴入肺炎链球菌建立肺炎感染模型，采用酶联免疫吸附法和实时定量PCR等方法，探讨扶正解毒法方药及其拆方对实验动物RORγt/ Foxp3免疫失衡的调控机制。本项目通过动物实验初步研究扶正解毒法对感染后免疫失衡的调控，为中药治疗肺炎提供实验依据。

肺炎感染后机体免疫稳态破坏，若感染控制不当可引起机体病理损伤甚至宿主死亡。感染后免疫稳态破坏与RORγt/ Foxp3失衡有关，课题组前期发现肺炎初期即存在"正虚"，提出"因虚致病"理论，扶正解毒法可调节机体免疫，减轻炎症损伤，从而发挥治疗作用，具体机制不详。本项目拟基于调控感染后免疫失衡开展研究，建立了大鼠气管内滴入肺炎链球菌的肺炎感染模型，并申请了实用新型专利：一种气管内给药装置（专利号：ZL 201420436500.5），然后采用酶联免疫吸附法和实时定量PCR等方法，探讨了扶正解毒法方药及其拆方对实验动物免疫失衡的调控机制。研究发现模型组大鼠RORγt显著升高，各中药组及西药组均降低，且与模型组相比较有统计学差异(P<0.05)；各组间比较有统计学差异(P<0.05)；模型组大鼠Foxp3显著降低，各中药组及西药组均升高，扶正解毒中药组及抗生素干预组与模型组相比较有统计学差异(P<0.05)；中医药能够抑制RORγt的过度表达，上调Foxp3的表达，从而调节使得Th17/Treg达到平衡，从而对机体起到保护作用。本项目初步通过动物实验初步研究扶正解毒法对感染后免疫失衡的调控，发表论文5篇，培养研究生1名，为中药治疗肺炎提供实验依据。