Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China, 410008.
BMC Complement Med Ther. 2022 Jul 13;22(1):186. doi: 10.1186/s12906-022-03663-5.
Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune inflammatory disease. Bi Zhong Xiao decoction (BZXD) performs multiple functions for rheumatoid arthritis (RA) treatment for decades. In this study, we aimed to study the protein alterations of BZXD in the early and late stages of RA.
Sprague-Dawley rats were randomly divided into the Control, collagen-induced arthritis (CIA) and BZXD groups. Clinical assessment, paw thickness, weight changes and serum inflammatory cytokine levels were used to evaluate anti-inflammatory effects. Histopathological tests were performed to assess the improvement of inflammation and synovial hyperplasia. Moreover, we analyzed the proteins profiling of synovial tissue samples with different time intervals after BZXD treatment by Isobaric Tag for Relative Absolute (ITRAQ) quantitative proteomics technology. To further explore the interrelationships among differentially expressed proteins (DEPs), we used DAVID Bioinformatics Resources v6.8 and STRING 11.0 for bioinformatics analysis. Besides, the western blot and immunohistochemistry were exerted to verify related proteins.
In our study, BZXD ameliorated joint inflammation, and suppressed the pathological changes in arthrosis of CIA rats. The proteomic analysis demonstrated that CIA rats were mainly involved in two significant pathways (the focal adhesion and the ECM-receptor interaction) in the early stage. BZXD down-regulated the expression of proteins involved in these pathways, such as CAV1, CHAD, COL3A1, COL5A2, COL6A1, and COL6A5. Additionally, BZXD exerts anti-inflammatory effects in the late stage mainly by increasing the expression of FASN and affecting fatty acid metabolism.
BZXD exerts therapeutic effects on RA through multi-pathways in the early and late stages. This work may provide proteomic clues for treating RA by BZXD.
类风湿关节炎（RA）是一种慢性、进行性、系统性自身免疫性炎症性疾病。痹肿消汤（BZXD）数十年来对类风湿关节炎（RA）的治疗具有多种作用。在这项研究中，我们旨在研究 BZXD 在 RA 早期和晚期的蛋白质变化。
将 Sprague-Dawley 大鼠随机分为对照组、胶原诱导性关节炎（CIA）组和 BZXD 组。临床评估、爪厚度、体重变化和血清炎症细胞因子水平用于评估抗炎作用。组织病理学检查用于评估炎症和滑膜增生的改善。此外，我们使用等重同位素标签相对和绝对定量（ITRAQ）定量蛋白质组学技术分析了 BZXD 治疗后不同时间间隔的滑膜组织样品的蛋白质谱。为了进一步探讨差异表达蛋白（DEPs）之间的相互关系，我们使用 DAVID 生物信息学资源 v6.8 和 STRING 11.0 进行生物信息学分析。此外，还进行了 Western blot 和免疫组化来验证相关蛋白。
在我们的研究中，BZXD 改善了 CIA 大鼠的关节炎症，并抑制了关节炎的病理变化。蛋白质组学分析表明，CIA 大鼠在早期主要涉及两个显著途径（粘着斑和细胞外基质-受体相互作用）。BZXD 下调了参与这些途径的蛋白质的表达，如 CAV1、CHAD、COL3A1、COL5A2、COL6A1 和 COL6A5。此外，BZXD 在晚期主要通过增加 FASN 的表达和影响脂肪酸代谢来发挥抗炎作用。
BZXD 通过早期和晚期的多途径对 RA 发挥治疗作用。这项工作可能为 BZXD 治疗 RA 提供蛋白质组学线索。
