“补肾益气清肺汤”主要成分黄芩苷通过抑制IL1R2影响肺腺癌复发转移的作用及机制研究

Lung cancer is still the most common malignant tumor with the highest morbidity and mortality in China.Recent studies have shown that the development of lung cancer is closely related to the inflammation caused by lung bacteria. "Bushen Yiqi Qingfei Decoction" can regulate HPA axis disorder and has significant anti-inflammatory effect. Previous studies and related studies have confirmed that baicalin has definite anti-tumor and anti-inflammatory effects. IL1R2 is an important link in regulating IL-1 system. It can not only inhibit local inflammatory response, but also promote the occurrence and development of various tumors, such as lung cancer. What is the specific mechanism of IL1R2 in influencing the process of lung cancer? By searching the domestic literature, we have not found any relevant reports. In addition, we found that baicalin can significantly inhibit the expression of IL1R2 by second-generation sequencing technology. Therefore, we speculate that baicalin can inhibit the occurrence and development of lung cancer by regulating IL1R2. In order to confirm this hypothesis, we will observe the effect of increasing or decreasing the expression of IL1R2 on the anti-cancer effect of baicalin and its possible signal transduction pathway at three levels, which will open up many promising ways for the intervention and treatment of lung cancer, provide a new basis for searching for a new anti-cancer mechanism of baicalin, and provide a new basis for "old medicine and new use"，and we expect to reveal the scientific basis of "Bushen Yiqi Qingfei Decoction" in the treatment of lung cancer.

肺癌仍是我国发病率、死亡率最高的恶性肿瘤。最新的研究表明肺癌的发展和肺部细菌引起的炎症密切相关。“补肾益气清肺汤”能调节HPA轴紊乱，有显著的抗炎作用，前期研究及相关研究中均证实了黄芩苷有明确的抗肿瘤、抗炎作用。IL1R2是调控IL-1系统的重要环节，不仅能抑制局部炎症反应，还能够促进各种肿瘤如肺癌的发生发展，那么IL1R2在影响肺癌过程的具体机制是什么？我们通过检索国内文献，尚未发现相关报道。另外我们用二代测序技术发现黄芩苷能明显抑制IL1R2表达，因此我们推测黄芩苷是通过调控IL1R2从而抑制肺癌的发生发展。为了证实这一假说，我们将三个层次，观察IL1R2表达增加或下调对黄芩苷抑癌作用的影响及可能影响的信号传导通路，将为肺癌的干预和治疗开辟多条有希望的途径，为寻找黄芩苷新的抑癌机制，为“老药新用”提供新的依据，从而进一步揭示“补肾益气清肺汤”治疗肺癌的科学依据。

最新的研究表明肺癌的发展和肺部细菌引起的炎症密切相关。“补肾益气清肺汤”有显著的抗炎作用，前期研究证实其主要组分黄芩苷有明确的抗肿瘤抗炎作用。IL1R2是调控IL-1系统的重要环节，不仅能抑制局部炎症反应，还能够促进各种肿瘤如肺癌的发生发展。通过检索国内文献，尚未发现IL1R2影响肺癌发展的具体机制相关报道。我们用二代测序技术发现黄芩苷能明显抑制IL1R2表达，推测黄芩苷是通过调控IL1R2从而抑制肺癌的发生发展。.首先利用shRNA 技术及慢病毒转染技术成功构建并筛选出 IL1R2 低表达细胞/ IL1R2 过表达稳定细胞株。然后通过实验观察 IL1R2 表达增加或下调后以及黄芩苷干预后肺癌细胞增殖迁移凋亡及炎症因子的影响。.通过细胞实验，我们发现IL1R2 过表达能促进肺癌细胞增殖迁移，而IL1R2 表达下调后肺癌细胞增殖迁移凋亡均受到明显抑制，IL-1β，IL6，TNF等相关炎症因子表达下降；黄芩苷干预后，过表达IL1R2组肺癌细胞增殖迁移凋亡炎症因子表达均受到明显抑制。通过动物实验，我们发现IL1R2 过表达组成瘤体积最大，有较多坏死组织血供丰富，说明IL1R2 能促进肺癌细胞增殖。IL1R2 表达下调后小鼠成瘤体积小，坏死组织少。黄芩苷干预后，小鼠肿瘤生长缓慢体积小。干扰组IL-1β，IL6，TNF等相关炎症因子表达下降；加入黄芩苷后，过表达IL1R2组肺癌细胞增殖迁移、凋亡、炎症因子表达均受到明显抑制。.因此，我们认为IL1R2可能通过调节 IL-1β，IL6，TNF等相关炎症因子从而影响肺癌细胞增殖、迁移、凋亡；黄芩苷干预后，IL1R2表达下降，IL-1β，IL6，TNF等相关炎症因子表达受到抑制，小鼠肿瘤生长缓慢，提示黄芩苷很可能通过抑制IL1R2表达从而发挥抗肿瘤作用。这一结果将为寻找黄芩苷新的抑癌机制，为“老药新用”提供新的依据，为深入挖掘中医药新的抑癌作用及机制提供物质基础。