低剂量的乙醇消费抑制了中性粒细胞外细胞陷的形成,以缓解类风湿性关节炎
Lin Jin1,2,3, Ziwei Zhang1,2,3, Pin Pan4
1Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, Anhui, China.
Communications biology
|October 26, 2023
概括
乙醇可以通过增加肠道微生物酸盐来保护类风湿性关节炎 (RA) 患者. 这种代谢物减少关节炎症和中性粒细胞活性,提供潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物组研究的研究.
- 代谢途径 代谢途径
背景情况:
- 类风湿性关节炎 (RA) 是一种慢性系统性自身免疫性疾病.
- 乙醇消费与减少RA发病率有关,但机制尚不清楚.
- 了解肠关节轴对于RA免疫调节至关重要.
研究的目的:
- 阐明乙醇影响RA的机制.
- 研究肠道微生物群及其代谢物在RA中的作用.
- 探索 RA 治疗的潜在治疗点.
主要方法:
- 乙醇给小鼠和分析肠道微生物群的组成.
- 测量微生物群代谢物酸盐水平.
- 在小鼠中诱导原诱导性关节炎 (CIA) 并评估关节炎的严重程度.
- 关于中性粒细胞活性和G蛋白结合受体43 (GPCR43) 信号传递的体外实验.
- 对肠道微生物群破坏的小鼠给予外源性酸盐.
主要成果:
- 乙醇治疗增加了小鼠的肠道Muribaculaceae和酸盐水平.
- 乙烯酸乙酸剂在CIA小鼠中减少了关节炎的严重程度.
- 乙酸盐降低了关节中性粒细胞和血清髓氧化酶-DNA复合体.
- 实验室研究表明,乙通过GPCR43调节中性粒细胞活性,减少内分泌网膜应激和中性粒细胞细胞外陷 (NET) 形成.
- 外源性乙改善了小鼠的肠道微生物失调和RA恶化.
结论:
- 肠道微生物代谢物酸在通过中性粒细胞调节来调节自身免疫性关节炎中起着至关重要的作用.
- 乙酸的机制涉及GPCR43,内质网膜应激和NET形成.
- 这些发现揭示了RA的肠关节轴,并表明乙酸作为一种潜在的治疗剂,可以在没有乙醇风险的情况下保护关节.
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