circPRKCE靶向TGF-β/Smad7通路抑制EMT参与落新妇苷防治放射性肺纤维化的作用及机制研究

放射性肺纤维化（RIPF）是放疗过程中常见的并发症，发病机制尚未完全阐明。我们前期发现肿节风提取物可通过抑制TGF-β/Smads信号通路介导的上皮间质转化进而防治RIPF。落新妇苷是肿节风提取物主要的活性成分之一，具有强抗炎抗氧化性，通过二代测序和生信分析研究落新妇苷处理后RIPF小鼠肺组织中circRNA，miRNA及mRNA表达谱的变化，发现circPRKCE、miR-15b-5p和Smad7之间可能存在竞争性内源RNA机制，落新妇苷可能通过调节circPRKCE靶向TGF-β/Smad7通路抑制上皮间质转化进而防治RIPF。本课题拟在此基础上通过体内外模型，运用RIP、双荧光素酶报告实验、腺相关病毒载体及挽救实验等研究手段，进一步揭示落新妇苷对RIPF的防护作用及分子机制，从非编码RNA水平为它防治RIPF提供新依据。

Radiation-induced pulmonary fibrosis (RIPF) is a common complication during radiotherapy, and the pathogenesis has not been fully elucidated. We previously discovered that Sarcandra glabra. Extract can prevent RIPF via EMT inhibition mediated by the TGF-β/Smads signaling pathway. Astilbin, one of the main active ingredients of Sarcandra glabra. Extract, has strong anti-inflammatory and antioxidant properties. The changes of circRNA, miRNA and mRNA expression profiles in lung tissues of RIPF mouse model with Astilbin treatment were studied by next-generation sequencing and bioinformatic analyses. It was found that there may be a competing endogenous RNA between circPRKCE, miR-15b-5p and Smad7, while Astilbin may prevent RIPF via EMT inhibition mediated by circPRKCE-targeted TGF-β/Smad7 signaling Pathway. On the above premises, we aim to investigate the effects and molecular mechanisms of Astilbin in prevent RIPF by a series of experiments, including RIP, dual-luciferase reporting experiment, adeno-associated virus vector and rescue experiment. We hope it can afford new basis for the anti-RIPF effects of Astilbin from the molecular perspective of circRNA.