芒柄花素-7-丹酚酸酯的制备及其抗肺纤维化作用机制的研究

项目名称： 芒柄花素-7-丹酚酸酯的制备及其抗肺纤维化作用机制的研究

项目编号： No.31470415

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 吕长俊

作者单位： 滨州医学院

项目金额： 85万元

中文摘要： 肺纤维化是一种机制未明的弥漫性肺间质疾病，近年由于雾霾的发生，其发病率逐年上升，目前仍无有效治疗方法。项目组在研究黄芪和丹参提取物的过程中发现，黄芪提取物中的芒柄花素和丹参提取物中的丹参素能减轻肺内胶原沉积，阻止纤维化进程。但芒柄花素水溶性差，生物利用度低、显效慢；丹参素化学稳定性差，易氧化、变色。为克服该缺陷，项目组运用天然产物化学技术制备得到新的化合物命名为芒柄花素-7-丹酚酸酯（简称SF），作为一种具有双前体药物性质的化合物，与芒柄花素相比水溶性增强；与丹参素相比稳定性增加。药理活性显示该化合物具有良好的抗肺纤维化作用，初步发现其作用机制与抑制肌成纤维细胞的分化、增殖和迁移相关。项目组研究发现长链非编码RNA-MRAK053938能够参与调控肌成纤维细胞的功能，本项目拟研究SF抗肺纤维化的作用及其MRAK053938参与的调控机制，为开发治疗肺纤维化药物和潜在的基因靶点提供理论依据。

中文关键词： 肺纤维化；长链非编码RNA；芒柄花素-7-丹酚酸酯；迁移；竞争性内源性RNA

英文摘要： Pulmonary fibrosis is one of interstitial lung diseases with unknown mechanism. Until now there has been no effective therapy. So it is important clinical value to research its pathogenesis and effctive treatment. In the process of extracting astragalus and salvia, we found that formononetin from astragalus extracts and danshensu from salvia extracts can reduce the collagen deposition in lung tissue and prevent the progress of fibrosis. But formononetin has a poor water solubility, low bioavailability and slow effect, and danshensu has a unstable chemical stability, oxidation and discoloration. To overcome these drawbacks, the project team product a new compound named formononetin -7 - sal ester (F-7-P) by natural medicine chemistry technology. Compared with formononetin and danshensu, the water-solubility and the stability are all improved. Pharmacological activity shows that the compound has a strong effect of anti-pulmonary fibrosis, and its mechanism of action relates to the inhibition of muscle fibroblast proliferation. The data shows that the long chain of non-coding RNA-MRAK053938 might be involved in its mechanism of anti-pulmonary fibrosis.The project aims to study the effect of F-7-P in anti-pulmonary fibrosis and the regulative mechanism of MRAK053938, and provide the data for developing new drugs and gene therapy for pulmonary fibrosis.

英文关键词： pulmonary fibrosis;long non-coding RNA;formononetin -7 - sal ester;migration;competing endogenous RNA