IL-17RA特异性核酸适配子诱导实验性关节炎小鼠滑膜细胞分化方向的研究  

Research on the differentiation direction of synovial cells induced by IL-17RA specific nucleic acid aptamer in experimental arthritis mice

作　　者：吴煌[1] 李永忠[1] 李冬青[2] 陈亮[3] WU Huang;LI Yongzhong;LI Dongqing;CHEN Liang(DepartmentⅠof Orthopedic Surgery,the Second People’s Hospital of Yichang,the Second People’s Hospital of China Three Gorges University,Hubei,Yichang 443000,China;School of Basic Medical Sciences,Wuhan University,Hubei,Wuhan 430000,China;Department of Sports Medicine,Renmin Hospital of Wuhan University,Hubei,Wuhan 430072,China)

机构地区：[1]湖北省宜昌市第二人民医院,三峡大学附属第二人民医院骨外一科,湖北宜昌443000 [2]武汉大学基础医学院,湖北武汉430000 [3]武汉大学人民医院运动医学科,湖北武汉430072

出　　处：《中国医药科学》2024年第11期13-16,37,共5页China Medicine And Pharmacy

基　　金：湖北省科技计划项目(2017CFB567)。

摘　　要：目的检测白细胞介素-17受体A(IL-17RA)特异性核酸适配子对实验性关节炎小鼠滑膜巨噬细胞(Mφ)和滑膜成纤维细胞(FLS)表型及功能的影响。方法手术切除小鼠膝关节内侧半月板,建立创伤性实验性关节炎的小鼠模型,检测IL-17RA特异性适配子RA10-6在体外对Mφ和FLS表型及功能的影响。结果一定剂量的RA10-6作用小鼠滑膜巨噬细胞以后,可以升高细胞分化簇CD206分子表达水平,降低CD16/32分子水平,差异有统计学意义(P<0.05);可促进巨噬细胞的人精氨酸酶1酶活性,同时对细胞诱导型一氧化氮合酶活性有一定的抑制作用;但是对CD163,树凝素-1分子影响不明显,差异无统计学意义(P>0.05)。在RA10-6的作用下,小鼠滑膜巨噬细胞的白细胞介素-10显著增加,转化生长因子-β呈一定程度增加,但是增幅没有白细胞介素-10明显,而白细胞介素-12显著降低。RA10-6作用小鼠滑膜成纤维细胞以后,可以升高CD248分子表达水平,差异有统计学意义(P<0.05),但是对CD90.5,血管细胞黏附分子-1影响不明显,差异无统计学意义(P>0.05)。该适配子对细胞尿苷二磷酸葡糖脱氢酶活性无明显影响,差异无统计学意义(P>0.05),但是对纤维连接蛋白的表达呈促进作用;在RA10-6的作用下,小鼠滑膜成纤维细胞的白细胞介素-6、趋化因子配体2、肿瘤坏死因子-α等细胞因子的影响差异无统计学意义(P>0.05)。结论IL-17RA特异性适配子RA10-6通过诱导滑膜巨噬细胞表型改变,降低炎性细胞因子的表达,抑制关节炎的进程。Objective To detect the impact of interleukin-17 receptor A(IL-17RA)specific nucleic acid aptamer on the phenotype and function of synovial macrophages(Mφ)and fibroblast-like synoviocytes(FLS)in experimental arthritis mice.Methods The medial meniscus of the knee joint in mice was surgically removed to establish a mouse model of traumatic experimental arthritis,and the impacts of IL-17RA specific nucleic acid aptamer RA10-6 on the phenotype and function of Mφand FLS in vitro were detected.Results After a certain dose of RA10-6 was administered to mouse synovial Mφ,the expression level of CD206 molecules in cell differentiation clusters was increased,while the level of CD16/32 molecules was reduced,with statistically significant differences(P<0.05).It could promote the enzymatic activity of human arginase-1 in Mφand inhibit the activity of cell-inducible nitric oxide synthase to a certain extent.However,the impacts on CD163 and DECTIN-1 molecules were not obvious,without statistically significant differences(P>0.05).Under the function of RA10-6,the levels of interleukin-10 in mouse synovial Mφsignificantly increased.There was a certain degree of increase in transforming growth factor-β,but the increase was not as obvious as interleukin-10.Meanwhile,interleukin-12 was significantly reduced.After RA10-6 acted on mouse synovial fibroblasts,the expression level of CD248 molecule could be increased,with statistically significant differences(P<0.05).However,the impact on CD90.5 and vascular cell adhesion molecule-1 was not obvious,without statistically significant differences(P>0.05).The aptamer had no obvious impact on the activity of cell uridine diphosphate glucose dehydrogenase,without statistically significant difference(P>0.05).However,it had a promoting function on the expression of fibronectin.Under the function of RA10-6,there were no statistically significant differences in the impacts of cytokines such as interleukin-6,chemokine ligand 2 and tumor necrosis factor-αon mouse synovial fibroblasts(P>0.05).C

关 键 词：适配子 白细胞介素-17受体A 白细胞介素-17 骨关节炎 

分 类 号：R684.3[医药卫生—骨科学]