Notch信号通路调控Th17/Treg平衡在香烟烟雾暴露大鼠肺损伤中的作用及千金苇茎汤干预机制

Smoking is one of the main inducing factors of severe pulmonary diseases. Cigarette smoke can lead to imbalance and dysfunction of Th17/Treg in lung and peripheral blood, which up regulate the expression level of Th17 cells and down regulate the expression level of Treg cells. COPD and respiratory inflammation induced by cigarette smoke are directly related to the immunological reaction and inflammatory response mediated by Th17/Treg cells, and these reactions can exist for a long time after quit smoking. The data indicate that Notch signaling pathway plays an important role in regulating the balance of Th17/Treg on airway inflammation. Qianjinweijing Decoction is a classic prescription of traditional Chinese Medicine which can clear away heat and toxic material, clear lung and eliminating phlegm, expel blood stasis and expelling pus. It is suitable for smoke poison lung treatment. The preliminary study of the research group shows that Qianjinweijing Decoction has the effect of regulating serum IL-17 and improving the pathological changes of lung tissue. Based on the above understanding, we speculate that Qianjinweijing Decoction can regulate the imbalance of Th17/Treg in cigarette smoke induced lung injury through Notch signaling pathway, so as to reduce smoking hazards. We expect to explore the molecular mechanism of reducing cigarette smoke damage by Qianjinweijing Decoction from animal model and cell level with molecular biology and cell biology techniques, hoping to provide a new target for the prevention of lung injury caused by cigarette smoke.

吸烟是多种严重肺部疾病主要诱发因素之一。香烟烟雾可以导致肺部及外周血中的Th17/Treg 平衡发生失调及功能紊乱，表现为Th17 细胞水平升高同时Treg 水平下调或功能降低。香烟烟雾诱导的COPD 及呼吸系统炎症与Th17/Treg细胞介导的免疫反应与炎症反应直接相关，且戒烟后可以长期存在。资料表明，Notch信号通路对Th17/Treg 平衡的调节在气道炎症疾病中起到重要作用。千金苇茎汤是中医经典的清热解毒，清肺化痰，逐瘀排脓方剂，符合烟毒伤肺的治则治法。课题组前期研究表明千金苇茎汤具有调节血清IL-17，改善肺组织病理的作用。基于以上认识，提出千金苇茎汤可通过Notch信号通路调控香烟烟雾肺损伤中Th17/Treg失衡，从而减轻吸烟危害的假说。拟从动物模型及细胞水平，运用分子生物学及细胞生物学技术，探讨千金苇茎汤干预香烟烟雾损伤的分子机制，为中医药预防香烟烟雾伤肺提供一个新的靶点。

吸烟是多种严重肺部疾病主要诱发因素之一，因此开展相关中医药预防干预吸烟相关疾病的研究具有重要的理论和临床意义。Notch信号通路对Th17/Treg 平衡的调节在气道炎症疾病中起到重要作用。千金苇茎汤（QJWJT）是中医经典的清热解毒，清肺化痰，逐瘀排脓方剂。课题运用了细胞生物学、分子生物学技术，探讨了千金苇茎汤通过Notch通路调节Th17/Treg平衡，为中医药预防干预慢性呼吸系统疾病研究提供了一个新靶点。.本课题研究表明：.1、QJWJT影响香烟烟雾暴露模型大鼠肺组织Th17/Treg分化及其相关细胞因子的表达。与模型组比较，QJWJT各剂量组干预后能够降低肺组织IL-17、IL-6浓度，同时提高IL-10的浓度。流式细胞术检测显示，QJWJT还能调节模型大鼠Treg/Th17比例，使Th17/Treg达到平衡状态。.2、QJWJT含药血清对烟雾处理的小鼠脾脏naïve 细胞上清液IL-17、IL-6、TGF-β及IL-10 影响。与烟雾模型组相比较，QJWJT高、中剂量组的IL-17浓度降低具有统计学意义；同样作为促炎因子的IL-6在高剂量组中有明显的降低。.3、QJWJT含药血清对烟雾处理的小鼠脾脏naïve 细胞分化Th17/Treg、RORγt、Foxp3mRNA 表达的影响。与模型组相比较，高剂量QJWJT组含药血清显示出明显降低Th17分化的趋势，高、中剂量含药血清组显示出增加Treg的分化。.4、QJWJT含药血清对烟雾处理的小鼠脾脏naïve 细胞分化Notch1、Jagged1、Jagged2、Delta-like 1、Delta-like 3、Delta-like 4 蛋白表达的影响。QJWJT含药血清的使用与Notch通道相关受体及Jagged1,2配体的低表达存在逆相关性，而与Delta-like受体存在一定的正相关。各剂量QJWJT含药血清组Notch和Jagged1表达均降低，中剂量下Jagged2表达降低。高剂量QJWJT含药血清组Delta-like1、3、4表达均显著升高。.结论：QJWJT能够从动物实验和细胞层面调节Notch信号通路，从而对Th17/Treg 平衡起到干预作用。