外周血miR-150-5p、SOCS1 mRNA对类风湿关节炎“病“”证”诊断意义的初步探讨  

The Value of miR-150-5p and SOCS1 MRNA on the Diagnosis of Rheumatoid Arthritis and the Differentiation of Traditional Chinese Medicine Syndrome Types

作　　者：邱明亮 朱卫娜[3] 莫丽莎[2] 徐卫东[2] 高波[4] Mingliang Qiu;Weina Zhu;Lisha Mo;Weidong Xu;Bo Gao(Clinical Medicine College,Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;Department of Rheumatology,The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;Department of pediatrics,The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;Department of Rheumatology,The Affiliated Changzhou Second People􀆳s Hospital of Nanjing Medical University,Changzhou 213003,China)

机构地区：[1]江西中医药大学临床医学院,南昌330006 [2]江西中医药大学附属医院风湿病科,南昌330006 [3]江西中医药大学附属医院儿科,南昌330006 [4]南京医科大学附属常州第二人民医院风湿免疫科,常州213003

出　　处：《世界科学技术-中医药现代化》2020年第6期2056-2062,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会地区基金项目(81860823):从cAMP-Rap2B-PLCε-IP3R/Ca2+信号通路介导的B细胞自噬途径探讨纳米雄黄治疗SLE的分子机制,负责人:徐卫东;江西省教育厅青年基金项目(GJJ190684):基于miR-150调控RA-FLS细胞SOCS1表达探讨益肾祛痹通络方治疗RA的机制研究,负责人:邱明亮。

摘　　要：目的探讨类风湿关节炎患者外周血miR-150-5p、细胞因子信号抑制因子1(suppressor of cytokine signaling 1,SOCS1)mRNA的表达及对类风湿关节炎(Rheumatoid Arthritis,RA)疾病诊断、中医证型判断的意义。方法纳入符合诊断标准的RA患者57例及健康对照组19例,根据《22个专业95个病种中医诊疗方案》有关RA的中医证候诊断标准,判断RA的中医证型。qPCR检测RA患者及健康对照组miR-150-5p、SOCS1mRNA的相对表达水平,同时检测血常规、肝功能、肾功能等常规指标。双荧光素酶分析方法判断两者是否存在靶向关系。统计分析miR-150-5p、SOCS1 mRNA对RA疾病的诊断意义及其与中医证型的相关性。结果RA患者外周血miR-150-5p的相对表达水平下调,低于正常人群(t=-19.019,P<0.05);其表达水平随疾病活动度升高,有下降趋势;患者外周血SOCS1 mRNA的相对表达水平上调,低于正常人群(t=5.333,P<0.05);其表达水平随疾病活动度升高,有上升趋势。MiR-150-5p与SOCS1 mRNA有靶向结合关系(P<0.05)。通过AUC曲线比较,miR-150-5p的相对表达水平区分RA的敏感性及特异性分别为98.1%、92.1%(AUC=0.972,P<0.05);SOCS1 mRNA的相对表达水平无法区分RA(AUC=0.472,P>0.05)。RA患者中miR-150-5p的相对表达水平低于3.06,RA患者风湿痹阻证、寒湿痹阻证的相对风险分别为8.33、250.00(P<0.05)。结论miR-150-5p、SOCS1 mRNA在RA患者中有差异性表达,且有靶向结合关系。miR-150-5p可能是RA的疾病诊断及中医风湿痹阻证、寒湿痹阻证证型诊断的潜在生物标志物。Objective To investigate the diagnosis value of miR-150-5 p on the diagnosis of rheumatoid arthritis(RA)and the differentiation of Traditional Chinese Medicine syndrome(TCM)types.Methods 57 cases of RA patients and 19 cases of healthy control(HC)people were enrolled in the study.The TCM syndrome types were differentiated,while the blood routine test,liver function and renal function were tested.qPCR was used to examine the expression level of peripheral blood SOCS-1 mRNA and miR-150-5 p.The binding site between suppressor of cytokine signaling 1(SOCS1)and miR-150-5 p was analyzed using European Bioinformatics Institute database,and the 3’UTR of SOCS1 mRNA,including the binding site,was amplified and ligated to the 3’-end of LUC2 gene in the pmirGL0 dualluciferase vector.The pmirGL0 vector and corresponding mimics were subsequently co-transfected into 293 T cells to compare the relative fluorescence intensity of LUC2 between the miR-150-5 p mimics and the negative control mimics groups.Furthermore,the value of the relative expression of miR-150-5 p on RA diagnose were analyzed by AUC,and on the TCM differentiation by Logistics regression analysis.Results Compared with HC group,the over-expression of SOCS1 mRNA and down-expression of miR-150-5 p were showed in the RA group(P<0.05).The diagnosis value is significant,with Youden index 3.06(sensitivity 0.981,specificity 0.920,AUC 0.972,P<0.05).It was showed that there was also a significant value on the differentiation of syndrome of wind-dampness and cold-dampness,with relative risk8.33,250.00,respectively.Conclusion The relative expression of miR-150-5 p and SOCS1 mRNA are dysregulated in RA patients.SOCS1 is a potential target of miR-150-5 p.MiR-150-5 p might be a valuable index on the diagnosis of RA and the differentiation of TCM syndromes of wind-dampness and cold-dampness.

关 键 词：miR-150-5p SOCS1 MRNA 类风湿关节炎 中医证型 

分 类 号：R255[医药卫生—中医内科学]