Department of Orthopaedics, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Bioengineered. 2022 May;13(5):11782-11793. doi: 10.1080/21655979.2022.2072055.
The study is aimed to determine the effects of cynarin (Cyn) on mice with gouty arthritis (GA) induced by monosodium urate (MSU). We measured swelling in the hind paws of mice using Vernier calipers and ultrasound. The liver, kidney, and hind paws were stained with hematoxylin-eosin, and M1 type macrophages were detected in the hind paws using anti-F4/80 and anti-iNOS antibodies. The mRNA expression of inflammatory factors in bone marrow-derived macrophages (BMDMs) and in the hind paws was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes and the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were analyzed via western blotting. Cyn was detected using Cell Counting Kit-8 (CCK-8). Cyn treatment reduced hind paw swelling and M1 macrophage infiltration, suppressed the mRNA expression of inflammatory factors, and inhibited NLRP3 inflammasome activation , in addition to inhibiting the phosphorylation of IKKa/β, p65, and c-Jun NH 2-terminal kinase (JNK). Furthermore, Cyn exerted anti-inflammatory and anti-swelling effects in mice with GA by regulating the NF-κB and JNK pathways and NLRP3 inflammasomes.
本研究旨在探讨水飞蓟宾(Cyn)对尿酸单钠(MSU)诱导的痛风性关节炎(GA)小鼠的作用。我们使用游标卡尺和超声测量小鼠后爪肿胀。用苏木精-伊红对肝、肾和后爪进行染色,用抗 F4/80 和抗 iNOS 抗体检测后爪 M1 型巨噬细胞。通过定量逆转录聚合酶链反应(qRT-PCR)检测骨髓来源的巨噬细胞(BMDMs)和后爪中炎症因子的 mRNA 表达。通过 Western blot 分析核苷酸结合寡聚化结构域(NOD)样受体(NLR)家族含pyrin 结构域蛋白 3(NLRP3)炎性体和核因子 kappa B(NF-κB)和丝裂原激活蛋白激酶(MAPK)途径。使用细胞计数试剂盒-8(CCK-8)检测 Cyn。Cyn 治疗可减轻后爪肿胀和 M1 巨噬细胞浸润,抑制炎症因子的 mRNA 表达,并抑制 NLRP3 炎性体激活,同时抑制 IKKa/β、p65 和 c-Jun NH 2 末端激酶(JNK)的磷酸化。此外,Cyn 通过调节 NF-κB 和 JNK 途径以及 NLRP3 炎性体发挥抗 GA 小鼠的抗炎和消肿作用。