基于ROS-ER stress-Ca2+信号通路研究健脾益肺II号减少COPD气道上皮细胞凋亡的作用机制

香烟烟雾诱导大量ROS产生，损伤气道上皮细胞，促进炎症反应和氧化还原失衡，导致COPD。其中，ER stress是一条重要的细胞凋亡途径。因此，基于ER stress，研究药物减少气道上皮细胞凋亡的作用机制，可为其治疗COPD提供科学依据。前期的药效学研究发现，健脾益肺II号能够减少COPD小鼠的气道和肺部炎症，缓解肺部的氧化还原失衡和蛋白酶-抗蛋白酶失衡。近期研究发现，健脾益肺II号能够减少COPD小鼠和CSE引起的气道上皮细胞的凋亡。本项目拟在前期工作基础上，利用体内和体外实验模型评价健脾益肺II号对COPD小鼠的气道上皮细胞凋亡和CSE刺激的气道上皮细胞凋亡的保护作用，并重点研究健脾益肺II号通过调节ROS-ER stress-Ca2+信号通路减少COPD气道上皮细胞凋亡的作用机制，为健脾益肺II号临床治疗COPD提供科学依据。

Cigarette smoke contains free radicals, oxidants and chemical components, which elevate the concentration of reactive oxygen species (ROS) produced enzymatically by epithelial cells. The production of additional ROS causes cell damage, and promotes inflammatory response and redox imbalance, leading to COPD. Among them, endoplasmic reticulum stress (ER stress) is an important apoptotic pathway. Therefore, based on ER stress, the mechanism investigation of drugs or herbal medicines on reducing apoptosis of bronchial epithelial cells can provide a scientific basis for the treatment of COPD. Previous studies had shown that Jianpiyifei II granule (JPYF II) possessed anti-inflammatory and antioxidative activities in a mouse model of COPD. In the present study, JPYF II exhibited anti-apoptotic effect in cigarette smoke-stimulated bronchial epithelial cells. On the basis of above work, our study will further focus on the effect and mechanism investigations of JPYF II on suppressing apoptosis in bronchial epithelial cells in COPD via inhibition of ROS-ER stress-Ca2+ signaling pathway, which will provide a theoretical basis for its clinical application.