赛达克斯通过抑制突中性粒细胞迁移来改善类风湿性关节炎:综合多奥米克分析的见解
Bingyang Xu1, Shuhan Liu1, Mingxie Chen1
1Chemistry and Biochemistry Laboratory, Guizhou Medical University, Guiyang, Guizhou 550025, China.
概括
赛达克斯 (SX) 通过阻断通过RAC1/PAK1通路的中性粒细胞迁移来抑制类风湿性关节炎 (RA). 这种传统的苗族草药配方通过调节免疫细胞活性,为RA提供了一种新的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 类风湿病学 类风湿病学
背景情况:
- 风湿性关节炎 (RA) 治疗结果往往是不令人满意的.
- 中性粒细胞迁移和激活是RA病理学的关键驱动因素.
- Sidaxue (SX) 的抗RA潜力已被认可,但其关于中性粒细胞迁移的机制尚不清楚.
研究的目的:
- 调查SX对RA中中性粒细胞迁移的影响.
- 阐明SX抗RA活性背后的分子机制.
主要方法:
- 集成的多omics (批量RNA-seq,scRNA-seq) 和门德尔随机化 (MR) 来识别目标.
- 使用UHPLC-MS对SX组件进行了表征,并通过分子对接评估了结合亲缘关系.
- 在体外 (血清分析) 和体内 (原诱导关节炎模型) 进行的功能研究.
主要成果:
- 多组和MR分析确定RAC1/PAK1通路对RA中性粒细胞迁移至关重要,PAK1被提名为药物标.
- SX含有与RAC1和PAK1.1具有高结合亲和力的化合物.
- 通过抑制RAC1/PAK1/LIMK1/Cofilin1轴,SX治疗的血清抑制了中性粒细胞迁移,NETs形成和细胞因子释放,这种效应在体内得到证实.
结论:
- 通过通过RAC1/PAK1/LIMK1/Cofilin1通路抑制中性粒细胞迁移和激活,SX可以改善RA.
- 这项研究揭示了SX的免疫调节机制,支持其作为天然RA治疗的潜力.
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