Tsai Chiau-Yuang, Shiau Ai-Li, Chen Shih-Yao, Chen Yu-Hung, Cheng Pai-Chiao, Chang Meng-Ya, Chen Dong-Hwang, Chou Chen-Hsi, Wang Chrong-Reen, Wu Chao-Liang
National Cheng Kung University, Tainan, Taiwan.
Arthritis Rheum. 2007 Feb;56(2):544-54. doi: 10.1002/art.22401.
Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen-induced arthritis (CIA) in rats.
Binding of 13-nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF-induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) in the ankle joints were determined.
Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF-induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold-treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFalpha and IL-1beta were also significantly reduced in the ankle joints of nanogold-treated rats.
Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.
血管生成在类风湿关节炎（RA）的发病机制中起作用，纳米金可抑制血管生成因子血管内皮生长因子（VEGF）的活性。因此，我们研究了关节内注射纳米金是否能改善大鼠胶原诱导的关节炎（CIA）。
评估13纳米的纳米金与人RA滑膜液（SF）中VEGF的结合情况及其对RA SF诱导的内皮细胞增殖和迁移的影响。在关节炎发作前，对患有CIA的大鼠进行关节内注射纳米金。通过临床、放射学和组织学变化的测量来监测CIA的进展。此外，还测定了踝关节的微血管密度、浸润巨噬细胞的程度以及肿瘤坏死因子α（TNFα）和白细胞介素-1β（IL-1β）的水平。
纳米金与RA SF中的VEGF结合，导致RA SF诱导的内皮细胞增殖和迁移受到抑制。与对照大鼠相比，纳米金治疗的CIA大鼠的踝关节周长、关节指数评分和放射学评分显著降低。此外，纳米金治疗大鼠的踝关节组织学评分（滑膜增生、软骨侵蚀和白细胞浸润）、微血管密度、巨噬细胞浸润以及TNFα和IL-1β水平也显著降低。
我们的结果首次证明关节内注射纳米金可改善大鼠CIA的临床病程。纳米金发挥了抗血管生成活性，随后减少了巨噬细胞浸润和炎症，从而减轻了关节炎。这些结果证明了纳米金作为治疗RA的新型治疗剂的原理。
