自然化合物库查发现用于治疗心脏纤维化和腹筋功能障碍的新分子
Katharina Schimmel1, Mira Jung1, Ariana Foinquinos1
1Institute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Circulation
|January 18, 2020
概括
研究人员发现天然来源的布法林和利科林是心肌纤维化的潜在治疗方法. 这些化合物在临床前模型中有效降低了纤维化,为新的心力衰竭治疗提供了希望.
科学领域:
- 心血管研究
- 药理学
- 自然产品化学
背景情况:
- 心肌纤维化是心脏重塑和心力衰竭的关键因素.
- 目前的临床策略缺乏针对心脏纤维细胞不适应反应的具体治疗方法.
- 开发新型抗纤维治疗药物对于全球治疗心力衰竭至关重要.
研究的目的:
- 发现和开发来自自然化合物的新型抗纤维疗法.
- 检查自然物质对心脏纤维化的有效性.
- 通过体外和体内机理学研究验证化合物.
主要方法:
- 在人心纤维细胞中对480种自然化合物的功能查.
- 评估抗增殖效应,细胞亡调节和细胞外基质表达.
- 在体内验证使用血管素II介导的小鼠和达尔盐敏感性心肌纤维化模型.
- 进行深度RNA测序以分析非编码RNAome变化.
主要成果:
- 对心脏纤维细胞具有抗增殖作用的15种化合物.
- 布法林 (类固醇) 和利科林 (类) 在体外和体内表现出强烈的抗纤维活性.
- 在高血压依赖的动物模型中改善了扩张功能;没有对肝脏或脏的毒性.
- 鉴定了保存的microRNA 671-5p和蛋白P1作为常见的下游效应物.
结论:
- 布法林和利科林是治疗心脏纤维化和心脏扩张功能障碍的有希望的候选药物.
- 这些天然化合物为治疗心力衰竭提供了潜在的治疗途径.
- 需要进一步研究它们的机制和临床应用.
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