基于TGF-β/Smad信号通路的中药莲子心抗肺纤维化物质基础及作用机制研究

项目名称： 基于TGF-β/Smad信号通路的中药莲子心抗肺纤维化物质基础及作用机制研究

项目编号： No.81503233

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 高颖

作者单位： 中国人民武装警察部队后勤学院

项目金额： 18万元

中文摘要： 特发性肺纤维化(IPF)是一种渐进性肺间质疾病，具有预后较差，病死率高的特点。近期研究证明传统用于治疗IPF的糖皮质激素及乙酰半胱氨酸无效，目前临床上缺乏有效的治疗药物。吡非尼酮（PFD）是全球首个获批治疗IPF的药物，其作用于TGF-β通路。我们研究发现中药莲子心总生物碱活性部位具有显著的抗IPF作用，可显著减少小鼠肺成纤维细胞增殖及胞外基质沉积，显著抑制小鼠TGF-βmRNA的表达；并且莲子心生物碱类成分具有与PFD相似的结构，因此有希望从莲子心获得与PFD结构及作用途径类似的新型抗IPF先导化合物。本项目建立基于荧光细胞成像技术的高内涵药物筛选系统，追踪莲子心抗IPF活性成分，从细胞-整体动物水平研究活性成分的抗IPF作用，利用RT-PCR、Western Blot等技术研究其对TGF-β/smad信号通路的影响，揭示莲子心抗IPF物质基础及作用机制，为研发新型抗IPF药物奠定基础。

中文关键词： 肺纤维化；TGF-β/Smad；；莲子心；物质基础；作用机制

英文摘要： Idiopathic pulmonary fibrosis(IPF) is a progressive interstitial lung disease，which is characterized by a poor prognosis as well as a high lethality. Recent studies have proved that conventional treatment of glucocorticoid and acetylcysteine are inefficient, and there have not been effective drugs to cure the IPF presently. Pirfenidone(PFD), which acts on the TGF-β pathway, is the first drug approved to treat IPF. Our studies found that total alkaloid of Plumula nelumbinis possess a remarkable effect of anti-lung fibrosis. It can significantly reduce the proliferation of the lung fibroblasts as well as accumulation of extracellular matrix of mice. In addition, the high expression of TGF-βmRNA was inhibited as well. The effect of total alkaloid of plumula nelumbinis is comparable to that of PFD. As alkaloids of liensinine share the same Pyridine structure with PFD , it is promising to find new leading compounds which are structurally and functionally similar to PFD. In this project, we establish cell level high content screening to screen active fractions and active compounds that have the anti-lung fibrosis effect. RT-PCR and Western Blot are employed in the investigation of compounds impact on the pathway of TGF-β/smad, explaining their material basis and mechanisms and providing a foundation for the development of novel anti-lung fibrosis drugs.

英文关键词： Idiopathic pulmonary fibrosis;TGF-β/Smad ;Lianzixin;Active substances;Machanisms