重离子辐射是肺癌放疗有效手段，但辐射诱发肿瘤相关骨髓间充质干细胞(BMSCs)遗传稳定性改变等旁效应影响其临床应用。中医认为BMSCs有元精属性，辐射属电离毒，可使营卫失调，伤及元精，BMSCs耗伤严重，易发突变。前期已证明益气补虚中药黄芪对肺癌相关BMSCs辐射旁损伤有显著防护作用。本课题拟探明CTSB/TGF-β/NF-κB旁效应关键通路在辐射肺癌相关BMSCs旁损伤中作用同时，借助分子对接技术从黄芪小分子库虚拟筛选可能与通路关键靶蛋白(CTSB、TGF-β、COX-2)结合的有效成分；蛋白微量热泳动及细胞生物学实验筛选有效成分及小分子最佳配伍；从动物、组织、细胞、分子水平探究其对重离子辐射肺癌细胞致BMSCs旁损伤的保护作用，揭示黄芪防护作用的物质基础及其多点显效、协同增效的分子机制；为基于CTSB/TGF-β/NF-κB通路筛选联合靶向小分子药物及黄芪联合辐射治疗肿瘤提供理论依据。

Heavy ion radiation is an effective method of radiotherapy for lung cancer, but radiation-induced bystander effects such as changes of genetic stability in tumor-associated bone marrow mesenchymal stem cells (BMSCs) affect its clinical application. Chinese medicine believes that BMSCs has the property of Yuanjing. Radiation belongs to ionizing poison which can cause barracks maladjustment and injury of Yuanjing. BMSCs is severely damaged and prone to mutagenesis after radiation. Previous studies has proved that Yiqi Buxu Chinese traditional medicine “Huangqi” has significant protective effect on radiation bystander injury of lung cancer-related BMSCs. The study aims to investigate the role of CTSB/TGF-β/NF-κB bystander effect pathway in BMSCs associated with lung cancer radiotherapy, and to use the molecular docking technique to virtually screen the active ingredients that can combine to the key target proteins (CTSB,TGF-β and COX-2) from the small molecular bank of Astragalus membranaceus; and to use protein microscale thermophoresis and cell biology experiments to screen the best combination of active ingredients and small molecules; to explore the protective effects of Astragalus membranaceus on bystander cell BMSCs induced by heavy ion radiation of lung cancer cells at the animal, tissue, cell and molecular levels; and to reveal the material basis of the protective effect of Astragalus membranaceus and the molecular mechanism of multi-point effect and synergy; which will provides a theoretical basis for the screening of targeted small molecule drugs based on CTSB/TGF-β/NF-κB pathway and the combination of Huangqi and radiation in the treatment of tumor.