目的检测白细胞介素(interleukin,IL)-17受体A(IL-17RA)特异性DNA适配子RA10-6对小鼠实验性关节炎的治疗作用。方法手术切除小鼠膝关节外侧半月板,建立外伤性实验性关节炎的小鼠模型。术后每周经关节腔注射适配子或其它药物对照,6周后观察膝关节病理标本,并检测滑膜组织IL-6,IL-8,IL-1β等细胞因子表达。结果 RA10-6能显著抑制关节炎小鼠滑膜增生,抑制小鼠滑膜组织IL-6的表达并呈剂量依赖性,与塞来昔布联用时抑制滑膜炎症的效果比单独使用更好。结论 RA10-6通过抑制IL-17与IL-17RA结合,抑制滑膜组织分泌IL-6,从而减轻关节炎小鼠的滑膜炎症。此外,RA10-6联合应用塞来昔布能达到更好的减轻滑膜炎症的效果,可作为一种辅助治疗关节炎的潜在药物。
Objective To detect the therapeutic effects of IL-17 RA specific DNA aptamers on the mouse model of experimental osteoarthritis( OA). Methods A meniscectomy was performed on Balb / C mice to generate an animal model of OA. All the mice received weekly intra-articular( i. a.) injections of aptamers or the control treatment for six weeks. The synovial membrane was evaluated by histomorphology and the mRNAs of critical inflammatory cytokines were measured by quantitative reverse transcriptasepolymerase chain reaction( RT-PCR). Results The histological examination and quantitative RT-PCR results showed that the OA mice that injected RA10-6, especially in combination with celecoxib,demonstrated an inhibition of synovial thickening and reduction of IL-6 level in the synovial tissue.Conclusion The results suggest that RA10-6 can inhibit synovial inflammation by blocking IL-17 / IL-17RA-mediated IL-6 expression.