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一种新的NRF2激活剂用于治疗人类代谢功能障碍相关的脂肪肝疾病

Adel Hammoutene^1,2, Samira Laouirem¹, Miguel Albuquerque^1,3

¹Université Paris Cité, Inserm, Centre de Recherche sur l'inflammation, F-75018, Paris, France.

JHEP reports : innovation in hepatology

|September 4, 2023

概括

一种新的NRF2激活剂S217879显示出治疗代谢相关脂肪肝疾病 (MAFLD) 的前景. 它在患者衍生的肝脏模型中减少了肝脏脂肪,炎症和纤维化,这表明临床试验的潜力.

科学领域:

肝病学肝病学是一种肝病学.
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

氧化应激是代谢相关脂肪肝疾病 (MAFLD) 和纤维化症的关键驱动因素.
核因子 (红色素衍生2) 类2 (NRF2) 是抗氧化反应的主调节者,也是MAFLD的潜在治疗点.
之前在动物身上进行的研究表明,NRF2激活可以防止MAFLD和纤维化.

研究的目的:

评估S217879新型NRF2激活剂在人类MAFLD中的治疗潜力.
调查S217879在患者获得的精密切割肝脏切片 (PCLS) 中作用的潜在机制.

主要方法:

来自12名MAFLD患者的人类PCLS被用S217879或elafibranor治疗了2天.
评估了安全性,疗效,肥胖症,肝损伤,炎症和纤维化.
研究的机制包括抗氧化剂反应,自和内质网膜压力.

主要成果:

S217879和elafibranor对人类MAFLDPCLS没有毒性.
这两种药物都提高了各自的基因 (S217879的NRF2,elafibranor的PPARα/δ).
S217879降低了甘油三,炎症,DNA损伤,亡,并抑制了纤维生成标记物,通过改善的脂质代谢,抗氧化剂反应和自作用来调解.

结论:

在人类PCLS模型中,S217879表明MAFLD具有显著的治疗潜力.
这些发现支持NRF2激活策略用于MAFLD治疗的临床评估.

关键词:

这是Elafibranor.纤维化纤维化纤维化炎症炎症是一种炎症.马夫尔德 (MAFLD) 是一个纳什·纳什 (Nash Nash) 是一个名为纳什的城市.这就是NRF2的NRF2.氧化应激是一种氧化应激.在PCLS中使用PCLS.在S21787979中,我们可以看到S217879的位置.

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