中文摘要
Th淋巴细胞亚群分化失衡是气道高反应(BHR)的重要机制,而IL-27在不同的体内微环境下可对Th1/Th2/Th17及Treg的分化倾向起促进或抑制作用,成为抗炎-促炎反应重要的调控机制之一。临床研究已证实射干麻黄汤对BHR及哮喘气道炎症具有良好的治疗作用,具体机制仍未完全阐明,文献回顾发现射干麻黄汤对炎症因子的调控与IL-27高度相似,推测“射干麻黄汤通过IL-27通路干预气道高反应Th亚群分化”治疗哮喘。本课题首先观察射干麻黄汤对Th亚群分化及IL-27分泌的影响,了解其对BHR小鼠抗炎-促炎反应的综合调控作用,重点探索射干麻黄汤对IL-27的可能调节通路,进一步观察射干麻黄汤对IL-27p28基因敲除小鼠的作用,寻找其对IL-27上下游通路的作用靶点。本课题首次在器官、细胞及分子水平上探讨射干麻黄汤对哮喘BHR的作用及机制,为哮喘BHR的防治提供新思路和药物作用新靶点。
英文摘要
The differentiation imbalance of Th lymphocyte subgroup is one of the most important mechanisms of bronchial hyperresponsiveness (BHR). IL - 27 drives Th1 / Th2 / Th17 and Treg differentiation positively or negatively depending on different microenvironment in vivo, which means significance to both anti- and pro-inflammatory response. Clinical studies have shown good treatment effect of Belamcanda and Ephedra Decoction on BHR and asthma airway inflammation, but the specific mechanism is still not elucidated. We reviewed the literature and discovered a highly similar influence between the decoction and IL – 27 on regulation of inflammatory markers. Our hypothesis is that " Belamcanda and Ephedra Decoction regulates the differentiation imbalance of Th lymphocyte subgroup through IL - 27 pathways in bronchial hyperresponsiveness". So we design the experiments. First we are going to observe the Th cells subgroup differentiation and IL – 27 secretion in BHR mice after intragastric administration of Belamcanda and Ephedra Decoction, and find its regulation on the anti- and pro-inflammatory response, especially the possible controlling pathways of IL – 27.Second we project the observation on IL-27p28-/-mice, to look for the regulatory targets of this decoction on IL – 27’s upstream or downstream pathways. This is the first time to explore the mechanism of Belamcanda and Ephedra Decoction on BHR through organ, cell and molecular level, and with this program going on, we will provide a novel theory and a potential pharmaceutical target in preventing and treating BHR and asthma.
