Department of Traditional Chinese Medicine, Liuzhou People's Hospital, No. 8 Wenchang Road, 545006, Liuzhou, Guangxi, China.
Class 3, Grade 2017, the First Clinical Medical Graduate School, Guangxi University of Traditional Chinese Medicine, 530001, Nanning, Guangxi, China.
Z Rheumatol. 2022 Mar;81(2):164-173. doi: 10.1007/s00393-020-00940-x. Epub 2020 Dec 15.
To compare the therapeutic efficacy of paclitaxel (PTX) alone to its combination with methotrexate (MTX) on rheumatoid arthritis.
A collagen-induced arthritis (CIA) rat model was established by induction of type II collagen. Rats were divided into blank control group, CIA model group, MTX group 1 mg/kg, PTX 1.5 mg/kg, PTX 2.5 mg/kg, PTX 3.5 mg/kg, and MTX 1 mg/kg + PTX 3.5 mg/kg, with 10 rats per group. The inflammation of the ankle joint was analyzed by H&E staining and interleukin (IL)-1β and IL‑6 expression was detected by immunohistochemistry. TUNEL assay was performed to detect synovial tissue cell apoptosis after administration of PTX and MTX either alone or in combination. TLR4 and p‑NF-κBp65 protein expression in synovial tissue and the changes of serum IL‑1β, IL‑6, IL‑12, MMP‑3, and TNFα protein factors were detected by western blot and ELISA, respectively.
PTX and MTX improved histopathological changes in CIA rats. Besides, the apoptosis rate of synovial tissue cells in the PTX 3.5 mg/kg group was more than that of the PTX + MTX group. Immunohistochemistry and western blot results indicated that PTX and MTX reduce the expression rate of IL‑6 and IL‑1β and downregulate TLR4 and p‑NF-κBp65 protein expression. Furthermore, TLR4 and p‑NF-κBp65 reduced the concentration of MMP‑3, IL‑12, IL‑6, IL1‑β, and TNFα.
Both PTX and MTX exert significant suppression on rheumatoid arthritis, and the combined effect of the two drugs is weaker than that of PTX alone. Moreover, intraperitoneal injection of PTX 3.5 mg/kg every other day was the optimal dose observed in this study.
比较紫杉醇（PTX）单独用药与联合甲氨蝶呤（MTX）治疗类风湿关节炎的疗效。
采用Ⅱ型胶原诱导关节炎（CIA）大鼠模型，将大鼠分为空白对照组、CIA 模型组、MTX 1mg/kg 组、PTX 1.5mg/kg 组、PTX 2.5mg/kg 组、PTX 3.5mg/kg 组和 MTX 1mg/kg+PTX 3.5mg/kg 组，每组 10 只。通过 H&E 染色分析踝关节炎症，免疫组化法检测白细胞介素（IL）-1β和 IL-6 表达。通过 TUNEL 检测单独或联合使用 PTX 和 MTX 后滑膜组织细胞凋亡。通过 Western blot 和 ELISA 检测滑膜组织 TLR4 和 p-NF-κBp65 蛋白表达以及血清中 IL-1β、IL-6、IL-12、MMP-3 和 TNFα 蛋白因子的变化。
PTX 和 MTX 改善 CIA 大鼠的组织病理学变化。此外，PTX 3.5mg/kg 组滑膜组织细胞凋亡率高于 PTX+MTX 组。免疫组化和 Western blot 结果表明，PTX 和 MTX 降低了 IL-6 和 IL-1β的表达率，并下调了 TLR4 和 p-NF-κBp65 蛋白表达。此外，TLR4 和 p-NF-κBp65 降低了 MMP-3、IL-12、IL-6、IL-1β和 TNFα 的浓度。
PTX 和 MTX 均对类风湿关节炎有显著抑制作用，两药联合作用弱于单独使用 PTX。此外，本研究观察到，每两天腹腔注射 3.5mg/kg 的 PTX 是最佳剂量。
