Department of Anesthesiology, The Second Xiangya Hospital, Central South University, 139 Ren-Min Road, Changsha, 410011, China.
Department of Anesthesiology, Hainan General Hospital, Haikou, 570311, Hainan, China.
Inflamm Res. 2019 Feb;68(2):147-155. doi: 10.1007/s00011-018-1202-3. Epub 2018 Nov 30.
The current study was intended to investigate the effect of ketamine (KET) on complete Freund's adjuvant (CFA)-induced arthritis in rats.
The CFA was administered in the hind paw of the rats for the induction of adjuvant-induced arthritis. The paw swelling of experimental animals was measured as hind paw volume. Hematoxylin and eosin staining was estimated and pathological changes in the joint tissues were observed under a light microscope. Furthermore, the bicinchoninic acid assay was used for protein quantification. The antibody-reactive bands were visualized using enhanced chemiluminescence.
The present study showed that KET significantly reduces the severity of arthritis in CFA mice. The therapeutic effects were linked with reduced joint swelling and destruction, as evidenced by analyzing rat paws. The KET also revealed to attenuate the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In western blot analysis, KET inhibit phosphorylation of MAPKs, IκBα and nuclear translocation NF-κB in the inflammatory joints of AIA rats. Moreover, KET showed to induce apoptosis via mitochondrial signalling pathways (Bcl2, Bax, cytochrome C, cleaved caspase-3 and cleaved caapse-9).
Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.
本研究旨在探讨氯胺酮（KET）对完全弗氏佐剂（CFA）诱导的大鼠关节炎的影响。
将 CFA 注射到大鼠后爪中以诱导佐剂性关节炎。实验动物的后爪肿胀程度通过后爪体积进行测量。采用苏木精和伊红染色法评估，并在光镜下观察关节组织的病理变化。此外，采用双缩脲法进行蛋白定量。使用增强化学发光法观察抗体反应带。
本研究表明，KET 可显著减轻 CFA 诱导的关节炎的严重程度。治疗效果与减轻关节肿胀和破坏有关，这可以通过分析大鼠爪子来证明。KET 还可以减轻促炎细胞因子（TNF-α、IL-1β、IL-6）的表达。在 Western blot 分析中，KET 抑制了 AIA 大鼠炎性关节中 MAPKs、IκBα 和核转位 NF-κB 的磷酸化。此外，KET 通过线粒体信号通路（Bcl2、Bax、细胞色素 C、cleaved caspase-3 和 cleaved caspase-9）诱导细胞凋亡。
综上所述，KET 通过多种机制显示出显著的抗类风湿关节炎活性，因此可能对 RA 具有治疗益处。
