【摘要】 目的 探讨系统性红斑狼疮(SLE)患者尿液外泌体微小RNA(miR)-146a和miR-181a的表达及其临床意义。方法 选取2023年1月至2023年10月四川大学华西医院诊断为SLE的患者40例作为SLE组，另同期的体检健康者20例作为对照组。根据SLE病情活动指数(SLEDAI)将SLE患者分为低活动组19例(SLEDAI≤9分)和高活动组21例(SLEDAI>9分)。采用实时荧光定量PCR检测尿液外泌体miR-146a和miR-181a表达，采用酶联免疫吸附试验(ELISA)检测血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、补体C3、IgG和抗心磷脂抗体(ACA)水平，采用受试者工作特征(ROC)曲线分析尿液外泌体miR-146a和miR-181a表达对SLE及SLE合并肾脏受累的诊断价值。结果 SLE组尿液外泌体miR-146a和miR-181a相对表达水平高于对照组(P<0.05),且高活动组尿液外泌体miR-146a和miR-181a相对表达水平高于低活动组(P<0.05)。肾脏受累的SLE患者的尿液外泌体miR-146a和miR-181a相对表达水平高于肾脏无受累的SLE患者(P<0.05)。高活动组血清IL-1β、IL-6、TNF-α、IgG和ACA水平高于低活动组，血清C3水平低于低活动组(P<0.05)。SLE患者的尿液外泌体miR-146a与血清IL-1β、IL-6、TNF-α、IgG和ACA水平呈正相关(r=0.443、0.493、0.410、0.381、0.340,P<0.05),与血清C3水平呈负相关(r=-0.340,P<0.05)。SLE患者的尿液外泌体miR-181a与血清IL-1β、IL-6、TNF-α、IgG和ACA水平呈正相关(r=0.342、0.470、0.373、0.371、0.334,P<0.05),与血清C3水平呈负相关(r=-0.368,P<0.05)。尿液外泌体miR-146a和miR-181a表达诊断SLE的曲线下面积分别为0.907、0.897(P<0.05),诊断SLE合并肾脏受累的曲线下面积分别为0.859和0.815(P<0.05)。结论 尿液外泌体miR-146a和miR-181a表达水平对SLE患者的疾病活动具有良好的评估作用，对SLE的病情预测和诊断具有潜在应用价值。更多还原

【Abstract】 Objective To investigate the expression and clinical significance of microRNA(miR)-146a and miR-181a in urine exosome of patients with systemic lupus erythematosus(SLE).Methods A total of 40 patients diagnosed with SLE at West China Hospital, Sichuan University from January 2023 to October 2023 were selected as the SLE group, and another 20 healthy individuals who underwent physical examinations during the same period were selected as the control group.According to SLE disease activity index(SLEDAI),SLE patients were divided into low activity group(19 cases, SLEDAI ≤ 9 scores) and high activity group(21 cases, SLEDAI > 9 scores).Real-time PCR was used to detect the expression of miR-146a and miR-181a in urine exosome, enzyme-linked immunosorbent assay(ELISA) was used to detect serum interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,complement C3,IgG and anti-cardiolipin antibody(ACA) levels, and receiver operating characteristics(ROC) curve was used to analyze the diagnostic value of miR-146a and miR-181a expression in urine exosome for SLE and SLE accompanied renal injury.Results The relative expression level of miR-146a and miR-181a in urine exosome in the SLE group was significantly higher than in the control group(P<0.05),and the relative expression level of miR-146a and miR-181a in urine exosome in the high activity group was significantly higher than in the low activity group(P<0.05).The relative expression level of miR-146a and miR-181a in urine exosome in SLE with renal injury was higher than in SLE without renal injury(P<0.05).The serum levels of IL-1β,IL-6,TNF-α,IgG and ACA in the high activity group were significantly higher than those in the low activity group, and the serum C3 level in the high activity group was significantly lower than that in the low activity group(P<0.05).miR-146a in urine exosome of SLE patients were significantly positively correlated with serum IL-1β,IL-6,TNF-α,IgG and ACA levels(r=0.443,0.493,0.410,0.381,0.340,P<0.05),and negatively correlated with serum C3 levels(r=-0.340,P<0.05).miR-181a in urine exosome of SLE patients were significantly positively correlated with serum IL-1β,IL-6,TNF-α,IgG and ACA levels(r=0.342,0.470,0.373,0.371,0.334,P<0.05),and negatively correlated with serum C3 levels(r=-0.368,P<0.05).The area under the curve of miR-146a and miR-181a in urine exosome for diagnosing SLE were 0.907 and 0.897,and the area under the curve of miR-146a and miR-181a in urine exosome for diagnosing SLE complicated with kidney damage were 0.859 and 0.815.Conclusion The expression levels of miR-146a and miR-181a in urine exosome have a good evaluation value for the disease activity of SLE,and have a potential application value for the prediction and diagnosis of SLE.更多还原