Department of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
College of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
J Biol Regul Homeost Agents. 2019;33(1):63-71.
Gout is a common metabolic disease and acute gouty arthritis (AGA) is one of the important complications. Jia-Wei-Si-Miao-Wan is a newly developed drug for treating acute gouty arthritis, but the molecular mechanism has not been completely clarified. Thus, this study was aimed to explore the regulation of Jia-Wei-Si-Miao-Wan on NLRP3 inflammasome and TLR/NF-κB signaling, which are two important signaling pathways in inflammation. AGA rat model was established by injecting monosodium urate into the right knee. Colchicine and Jia-Wei-Si-Miao-Wan were administrated by gavage. The circumference of the knee was measured. IL-1β and IL-18 level in the flushing fluid was detected by enzyme linked immunosorbent assay (ELISA). Western blot, immunohistochemistry and quantitative real-time RT-PCR were used to detect the protein and mRNA expression of TLR4, NLRP3, ASC, caspase-1, NF-κB and p-NF-κB. The results showed that IL-1β and IL-18 level in the flushing fluid was increased and TLR4, NLRP3, ASC, caspase-1, NF-κB and p-NF-κB expressions were up-regulated after the establishment of AGA rat model. Colchicine and Jia-Wei-Si-Miao-Wan administration could alleviate the inflammation in the knee by inhibiting NLRP3 inflammasome and TLR/NF-κB signaling. In vivo data showed that the therapeutic effect of Jia-Wei-Si-Miao-Wan could be comparable with colchicine but had lower hepatic and renal toxicity. In conclusion, Targeting NLRP3 inflammasome and TLR/NF-κB signaling by Jia-Wei-Si-Miao-Wan could be effective in treating AGA.
痛风是一种常见的代谢性疾病，急性痛风性关节炎（AGA）是其重要并发症之一。加味四妙丸是一种新开发的治疗急性痛风性关节炎的药物，但分子机制尚未完全阐明。因此，本研究旨在探讨加味四妙丸对 NLRP3 炎性体和 TLR/NF-κB 信号通路的调节作用，这两条信号通路是炎症中的两个重要信号通路。通过向右侧膝关节注射单钠尿酸盐建立 AGA 大鼠模型。通过灌胃给予秋水仙碱和加味四妙丸。测量膝关节的周长。通过酶联免疫吸附试验（ELISA）检测灌洗液中 IL-1β 和 IL-18 的水平。Western blot、免疫组织化学和实时定量 RT-PCR 用于检测 TLR4、NLRP3、ASC、caspase-1、NF-κB 和 p-NF-κB 的蛋白和 mRNA 表达。结果表明，AGA 大鼠模型建立后，灌洗液中 IL-1β 和 IL-18 的水平升高，TLR4、NLRP3、ASC、caspase-1、NF-κB 和 p-NF-κB 的表达上调。秋水仙碱和加味四妙丸给药可通过抑制 NLRP3 炎性体和 TLR/NF-κB 信号通路减轻膝关节炎症。体内数据表明，加味四妙丸的治疗效果可与秋水仙碱相媲美，但肝肾功能毒性较低。总之，加味四妙丸通过靶向 NLRP3 炎性体和 TLR/NF-κB 信号通路可有效治疗 AGA。
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