摘要
目的Toll样受体(TLR)4是NF-kB信号通路的重要调节因子,被认定为miRNA-93的直接靶标。文章探究MicroRNA-93(miRNA-93)和TLR4在类风湿关节炎(RA)患者血清中的表达情况以及临床意义。方法回顾性分析2020年4月至2021年4月于上海中医药大学附属曙光医院风湿免疫科诊治的82例RA患者临床资料。依据28个关节疾病活动度评分(DAS28)将RA患者进一步分组。DAS28>5.1者纳入高活动组(n=42),2.6<DAS28≤5.1分者纳入中低活动组(n=40);另选取同期健康体检者38例作为对照组。采用实时荧光定量PCR(qRT-PCR)法检测外周血miRNA-93和TLR4的表达水平,ELISA法检测血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶3(MMP-3)表达水平,分析血清miRNA-93、TLR4、IL-6、TNF-α、MMP-3之间的关系,评价血清miRNA-93、TLR4在RA疾病诊断中的效能。结果高活动组、中低活动组患者血清miRNA-93表达水平均低于对照组,TLR4表达水平均显著高于对照组(P<0.05);高活动组患者血清miRNA-93表达水平低于中低活动组,TLR4表达水平高于中低活动组(P<0.05)。高活动组、中低活动组的IL-6、TNF-α、MMP-3表达水平均较对照组更高(P<0.05),高活动组患者IL-6、TNF-α、MMP-3表达水平均高于中低活动组(P<0.05)。RA患者血清miRNA-93和TLR4表达呈负相关(r=-0.0.518,P=0.000)。血清miRNA-93与IL-6、TNF-α、MMP-3水平均呈负相关(r=-0.437、-0.329、-0.541,P<0.05);血清TLR4与IL-6、TNF-α、MMP-3水平均呈正相关(r=0.543、0.437、0.462,P<0.05)。血清miRNA-93诊断RA的AUC为0.72,敏感度与特异度分别为79.27%和68.42%;血清TLR4诊断RA的AUC为0.723,敏感度与特异度分别为47.56%和92.11%;血清miRNA-93联合TLR4诊断RA的AUC为0.81,敏感度与特异度分别为81.60%和65.34%,两者联合诊断的效能均优于单独血清miRNA-93、TLR4诊断(Z=2.137、2.458,P=0.032、0.029)。IL-6、TNF-α、MMP-3诊断RA的AUC分别为0.785、0.797、0.756(P<0.05)。结论RA患者血清miRNA-93表达降低,TLR4表达升高。两者联合检测有助于RA疾病的诊断。
Objective Toll-like receptor 4(TLR4),an important regulator of NF-kB signaling pathway,has been identified as the direct target of miRNA93.This paper was to investigate the expression of MicroRNA93(miRNA93)and TLR4 in serum of patients with rheumatoid arthritis(RA)and their clinical significance.Methods Clinical data of 82 patients with RA diagnosed and treated in the Department of Rheumatology and Immunology of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2020 to April 2021 were retrospectively analyzed.Patients with RA were further grouped according to 28 joint disease activity scores(DAS28).Those with DAS28>5.1 were included in the high activity group(n=42),while those with 2.6<DAS28≤5.1 were included in the middle and low activity group(n=40).Another 38 healthy subjects were selected as control group.The expression levels of miRNA93 and TLR4 in peripheral blood were detected by real-time quantitative PCR(qRT-PCR),and the expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and matrix metalloproteinase 3(MMP3)in serum were detected by ELISA.The relationship between serum miRNA93,TLR4,IL-6,TNF-αand MMP3 was analyzed to evaluate the efficacy of serum miRNA93 and TLR4 in the diagnosis of RA disease.Results Serum miRNA93 expression level in high activity group and low activity group was lower than that in control group,and TLR4 expression level was significantly higher than that in control group(P<0.05).High activity group of patients serum miRNA 93 expression level is lower than the low activity group,TLR4 expression level was higher than low activity group(P<0.05).The expression levels of IL-6,TNF-αand MMP3 in high activity group and low activity group were higher than those in control group(P<0.05),and the expression levels of IL-6,TNF-αand MMP3 in high activity group were higher than those in low activity group(P<0.05).RA patients serum miRNA 93 and TLR4 expression showed a negative correlation(r=-0.518,P=0.000).Serum miRNA 93 and IL6 and negatively correlated with the level of TNF alpha,MMP3(r=0.437,0.329,0.541,P<0.05);Serum TLR4 was positively correlated with the levels of IL-6,TNF-αand MMP3(r=0.543,0.437,0.462,P<0.05).The AUC of serum miRNA93 in the diagnosis of RA was 0.72,the sensitivity and specificity were 79.27%and 68.42%,respectively.The AUC of serum TLR4 in the diagnosis of RA was 0.723,and the sensitivity and specificity were 47.56%and 92.11%,respectively.The AUC of serum miRNA93 combined with TLR4 in the diagnosis of RA was 0.81,and the sensitivity and specificity were 81.60%and 65.34%,respectively.The efficacy of the combined diagnosis was superior to that of serum miRNA93 and TLR4 alone(Z=2.137,2.458,P=0.032,0.029).The AUC of IL-6,TNF-αand MMP3 in the diagnosis of RA were 0.785,0.797 and 0.756,respectively(P<0.05).Conclusion Serum miRNA93 expression was decreased and TLR4 expression was increased in RA patients.The combination of the two tests is helpful for the diagnosis of RA disease.
作者
杨光月
杜国庆
潘富伟
杨宗睿
YANG Guang-yue;DU Guo-qing;PAN Fu-wei;YANG Zong-rui(Department of Orthopedics and Traumatology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《医学研究生学报》
CAS
北大核心
2022年第11期1166-1170,共5页
Journal of Medical Postgraduates
基金
国家自然科学基金(82174403)。
