黄芩清热除痹胶囊通过调节肠道菌群、改善肠道屏障抑制类风湿性关节炎。
Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.
发表日期:2024
作者:
Yanhui Peng, Yurong Huang, Hui Li, Chen Li, Yajie Wu, Zhe-Sheng Chen, Xiao Wang, Faxue Liao, Chenggui Miao
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
临床前和确诊的类风湿性关节炎(RA)患者肠道菌群和肠道屏障的变化表明肠道菌群和肠道屏障在RA的诱导和持续过程中发挥着重要作用。黄芩清热除痹胶囊(HQC)是临床上治疗RA有效的中药方剂,但其治疗机制尚未完全阐明。本研究采用实时荧光定量PCR(RT-qPCR)、16SrRNA测序、Western blot(WB) )、免疫荧光等方法探讨HQC是否抑制RA。基于小鼠胶原诱导关节炎(CIA)模型、人结肠癌细胞系(Caco-2)和来自成纤维细胞样滑膜细胞(FLS)的研究在RA患者中,我们发现CIA模型组肠道菌群紊乱,肠道屏障受损,脂多糖(LPS)水平升高,而HQC可以调节肠道菌群和肠道屏障,减少LPS转入血液。抗生素耗尽削弱了 HQC 的抗 RA 作用,而 HQC 粪便微生物群移植减轻了 RA 病理。此外,LPS可增加RA病理因子MMP3、纤连蛋白和炎症因子IL-6、TNF-α、IL-1β和IL-8的表达,表明外周血LPS水平升高与RA病理相关。肠道菌群和肠道屏障的破坏是RA发生的重要因素。 HQC 通过调节肠道菌群、肠道屏障和抑制 LPS 转入血液来改善 RA。该研究揭示了RA的新发病机制,为推进RA的HQC治疗奠定了科学基础。版权所有©2024 Peng, Huang, Li, Li, Wu, Chen, Wang, Liao and Miao。
Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified.In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA.Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1β and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology.The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.Copyright © 2024 Peng, Huang, Li, Li, Wu, Chen, Wang, Liao and Miao.