淫羊藿次苷Ⅱ通过RelA-LncRNA H19途径 调控VSMC功能抑制血管负性重塑的机制研究

血管负性重塑是人们长期关注但尚未解决的难题，现有药物疗效不佳。LncRNA H19介导 VSMC病理性增殖和表型转化是血管负性重塑的关键，课题组发现转录因子RelA与LncRNA H19启动子存在结合位点；并实验证明淫羊藿次苷II可下调RelA表达，同时抑制血管负性重塑；提示淫羊藿次苷II可能通过干预RelA-LncRNA H19途径抑制血管负性重塑。本项目拟在细胞及转基因鼠水平明确：淫羊藿次苷Ⅱ干预血管负性重塑与调控RelA、LncRNA H19表达的相关性；RelA-LncRNA H19途径构成的分子基础及其在血管负性重塑中的作用；淫羊藿次苷Ⅱ通过RelA-LncRNA H19途径干预血管负性重塑的分子机制及靶向特征；本项目从药物、转录因子、非编码RNA表观遗传调控的三维角度，阐明淫羊藿次苷II抑制血管负性重塑的药理学机制，为发掘血管负性重塑抑制剂、优化此类疾病治疗策略提供新思路。

Negative vascular remodeling has long been a critical issue and an unsolved problem, all the known drugs have poor clinical efficacy. VSMC pathological proliferation and phenotype switching mediated by LncRNA H19 is crucial in negative vascular remodeling. We have found potential binding sites between transcription factor RelA and LncRNA H19 promoter region. We further proved icariside II could reduce RelA expression and inhibit negative vascular remodeling, which indicates icariside II might inhibit negative vascular remodeling through RelA-LncRNA H19 pathway. In the project, both cell and transgenic mice will be used to explore the hypotheses: The relationship between icariside II inhibiting negative vascular remodeling and icariside II regulating expression of RelA as well as LncRNA H19; The molecular basic of RelA-LncRNA H19 pathway and function in negative vascular remodeling; The molecular mechanism and targeting characteristic of icarside II mediating negative vascular remodeling and intervening RelA-LncRNA H19 pathway; This study aimed to illuminate pharmacological mechanism of icariside II preventing negative vascular remodeling with drug, transcription factor and non-coding RNA epigenetic regulation, which has great potential in developing inhibitor of negative vascular remodeling and optimizing therapeutic regimen.