摘要
目的检测SLE患者PBMCs中微RNA-223(miR-223)及核苷酸结合寡聚化结构域(NOD)样受体家族蛋白3(NLRP3)炎性小体组分[NLRP3、凋亡相关的斑点样蛋白(ASC)、胱天蛋白酶(caspase)-1]mRNA表达水平,探讨其在SLE发病中的作用及临床意义。方法实时荧光定量PCR技术检测35例初诊SLE患者、30名健康对照及20例治疗后SLE患者PBMCs中miR-223及NLRP3炎性小体组分mRNA表达量,采用χ2和t检验进行统计学分析;采用Pearson检验分析SLE患者miR-223及NLRP3炎性小体组分mRNA表达水平与抗dsDNA抗体、抗核小体抗体(AnuA)、ESR、SLEDAI的相关性。结果SLE患者PBMCs中miR-223、caspase-1mRNA表达水平高于健康对照[(1.17±0.15)和(0.68±0.14),t=2.416,P=0.0186;(1.89±0.13)和(1.32±0.13),t=3.123,P=0.0027],NLRP3、ASCmRNA表达水平低于健康对照[(0.64±0.05)和(0.98±0.06),t=4.442,P<0.01;(0.98±0.08)和(1.32±0.12),t=2.391,P=0.0198];相关分析显示SLE患者PBMCs中miR-223mRNA表达水平与NLRP3mRNA表达水平呈负相关(r=-0.7849,P<0.05),而与ASC、caspase-1mRNA表达水平无相关性;SLE患者PBMCs中miR-223mRNA表达水平与抗dsDNA抗体、ESR、SLEDA呈正相关(r=0.7035、0.6923、0.6873,P均<0.05),与AnuA无相关性;给予药物治疗后,SLE患者PBMCs中miR-223、caspase-1mRNA表达水平明显降低[(1.30±0.22)和(0.79±0.11),t=2.07,P=0.0453;(2.05±0.19)和(1.50±0.11),t=2.471,P=0.0183],NLRP3mRNA表达水平明显升高[(0.69±0.08)和(0.94±0.07),t=2.445,P=0.0193];在LN患者与SLE无肾损害患者PBMCs中miR-223mRNA表达水平差异无统计学意义。结论miR-223、caspase-1在SLE患者PBMCs中呈高表达,NLRP3、ASC在SLE患者PBMCs中呈低表达,miR-223mRNA表达水平与NLRP3mRNA表达水平呈负相关,且SLE患者PBMCs中miR-223mRNA的表达水平与疾病活动呈正相关,治疗后miR-223mRNA表达水平明显下降,提示miR-223可能在SLE发病中扮演重要角色。
Objective To determine the mRNA levels of microRNA-223 (miR-223) and NLRP3 in-flammasome components [Nod-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1] in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) and to explore its clinical significance. Methods Real time polymerase chain reaction (PCR) was used to detect the mRNAlevels of miR-223 and NLRP3 inflam-masome components in PBMCs from 35 SLE patients, 30 healthy controls and 20 SLE patients after treatment, and then their correlations with clinical and laboratory parameters [anti-double-stranded deoxyribon-ucleic acid (dsDNA) antibody, anti-nucleosome antibody (AnuA), erythrocyte sedi-mentation rate (ESR)] were evaluated. Data were analyzed using t test or χ2 test and Pearson test was used for correlation analysis. Results Com-pared with healthy controls, mRNA levels of miR-223 and Caspase-1 were higher in the PBMCs from SLE patients [(1.17±0.15) vs (0.68±0.14), t=2.416, P=0.018 6;(1.89±0.13) vs (1.32±0.13), t=3.123, P=0.002 7], but the NLRP3 and ASC mRNA expression levels were in the opposite [(0.64±0.05) vs (0.98±0.06), t=4.442, P<0.01;(0.98±0.08) vs (1.32±0.12), t=2.391, P=0.019 8]. Correlation analysis results showed that there was a negative correlation of mRNA levels between the miR-223 and NLRP3 (r=-0.784 9, P<0.05), but the miR-223 had no correlation with ASC and caspase-1. The mRNA levels of miR-223 was positively correlated with anti-dsDNA antibody, SLEDAI and ESR (r=0.703 5, 0.692 3, 0.687 3, all P values<0.05), but had no correlation with AnuA. After treatment, the mRNA expression of miR-223 and caspase-1 in PBMCs from SLE patients was significantly reduced [(1.30±0.22) vs (0.79±0.11), t=2.07, P=0.045 3;(2.05±0.19) vs (1.50±0.11), t=2.471, P=0.018 3], while the mRNA level of NLRP3 increased [(0.69±0.08) vs (0.94±0.07);t=2.445, P=0.019 3]. There was no significant difference in the expression of miR-2
作者
麻贞贞
赵萍
吕继彩
孙红胜
杨清锐
Ma Zhenzhen;Zhao Ping;Lyu Jicai;Sun Hongsheng;Yang Qingrui(Department of Rheumatology and Immunology,Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,China)
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2019年第1期10-14,共5页
Chinese Journal of Rheumatology
基金
国家自然科学基金面上项目(81671605).
