狼疮性肾炎患儿外周血单个核细胞miR-151a-3p的表达及其与疾病活动度和血管损害的相关性

Expression of miR-151a-3p in peripheral blood mononuclear cells of children with lupus nephritis and its correlation with disease activity and vascular damage

目的探讨狼疮性肾炎(LN)患儿外周血单个核细胞(PBMC)miR-151a-3p的表达及其与疾病活动度和血管损害的相关性。方法选取2016年1月至2019年3月海南省妇女儿童医学中心收治的LN患儿87例,其中Ⅱ型16例、Ⅲ型14例、Ⅳ型34例、Ⅴ型17例、Ⅵ型6例;另选取健康体检儿童40例作为健康对照组。采用系统性红斑狼疮病情活动指数(SLEDAI)评分将87例LN患儿分为LN稳定组(31例)、LN活动组(56例);根据不同中膜比例分为轻度组25例,中度组34例,重度组28例。采用实时荧光定量PCR(qPCR)法检测PBMC中miR-151a-3p表达水平,Pearson相关分析PBMC中miR-151a-3p表达水平与SLEDAI评分及肾间质损害评分的相关性。结果LN组、LN活动组和LN稳定组miR-151a-3p(0.47±0.06、0.30±0.04、0.75±0.12比1.62±0.35)表达水平均明显低于健康对照组(均P<0.01),且LN活动组miR-151a-3p表达水平明显低于LN稳定组(P<0.01)。LN活动组SLEDAI评分[(14.35±4.60)分比(8.25±2.24)分]及肾间质损害评分[(52.70±6.30)分比(34.80±4.10)分]均明显高于LN稳定组(均P<0.01)。Ⅴ~Ⅵ型组和Ⅳ型组miR-151a-3p(0.18±0.02、0.41±0.05比0.83±0.16)表达水平均明显低于Ⅱ~Ⅲ型组(均P<0.01)。Ⅴ~Ⅵ型组和Ⅳ型组SLEDAI评分[(16.50±5.28)分、(12.36±3.74)分比(6.40±1.70)分]及肾间质损害评分[(62.70±7.40)分、(47.20±5.80)分比(25.80±3.50)分]均明显高于Ⅱ~Ⅲ型组(均P<0.01)。重度组、中度组和轻度组患儿miR-151a-3p(0.20±0.02、0.39±0.04、0.86±0.18比1.62±0.35)表达水平均明显低于健康对照组(均P<0.01),且随着血管损害程度加重,miR-151a-3p表达水平降低。重度组和中度组SLEDAI评分[(15.20±5.10)分、(12.85±3.90)分比(6.70±1.82)分]及肾间质损害评分[(57.30±6.80)分、(51.60±6.30)分比(27.20±3.60)分]均明显高于轻度组(均P<0.01)。LN患儿miR-151a-3p表达水平与SLEDAI评分及肾间质损害评分均呈负相关(r=-0.682、-0.627,均P<0.001)。结论LN患儿PBMC中miR-151a-3p表达水平明显降低,且其水平降低与疾病活动度及血管损害程度密切相关,可能参与了LN的发生发展。

Objective To investigate the expression of miR-151a-3p in peripheral blood mononuclear cells(PBMCs)of children with lupus nephritis(LN)and its correlation with activity and vascular damage.Methods A total of 87 children with LN admitted in Hainan Women and Children′s Medical Center from January 2016 to March 2019 were enrolled,including 16 cases of typeⅡ,14 cases of typeⅢ,34 cases of typeⅣ,17 cases of typeⅤand 6 cases of typeⅥ.Besides,additional 40 children with normal physical examination were selected as the healthy control group.The 87 children with LN were divided into the LN stable group(31 cases)and LN active group(56 cases)by using systemic lupus erythematosus disease activity index(SLEDAI)scores.According to different proportions of the medium membrane,the patients were classified into the mild group(25 cases),moderate group(34 cases)and severe group(28 cases).Real time quantitative PCR(qPCR)was used to detect the expression level of miR-151a-3p in PBMCs of each group.The correlation of the expression level of miR-151a-3p in PBMCs of LN children with the SLEDAI score and renal interstitial damage score was studied by Pearson correlation analysis.Results The expression levels of miR-151a-3p in the LN group,LN active group and LN stable group(0.47±0.06,0.30±0.04,and 0.75±0.12,respectively)were significantly lower than that in the healthy control group(1.62±0.35)(all P<0.01),and the expression level of miR-151a-3p in the LN active group(0.30±0.04)was significantly lower than that in the LN stable group(0.75±0.12)(P<0.01).The SLEDAI score[(14.35±4.60)points vs.(8.25±2.24)points]and renal interstitial damage score[(52.70±6.30)points vs.(34.80±4.10)points]in the LN active group were significantly higher than those in the LN stable group(all P<0.01).The expression levels of miR-151a-3p(0.18±0.02,0.41±0.05 vs.0.83±0.16)in typeⅤ-Ⅵand typeⅣgroups were significantly lower than that in the typeⅡ-Ⅲgroup(all P<0.01).The SLEDAI scores[(16.50±5.28)points,(12.36±3.74)points vs.(6.40±1.70)points]and renal interstitial damage scores[(62.70±7.40)points,(47.20±5.80)points vs.(25.80±3.50)points]in typeⅤ-Ⅵand typeⅣgroups were significantly higher than those in the typeⅡ-Ⅲgroup(all P<0.01).The expression levels of miR-151a-3p(0.20±0.02,0.39±0.04,0.86±0.18 vs.1.62±0.35)in severe,moderate and mild groups were significantly lower than that in the healthy control group(all P<0.01),and the expression level of miR-151a-3p decreased with the aggravation of vascular damage.The SLEDAI scores[(15.20±5.10)points,(12.85±3.90)points vs.(6.70±1.82)points]and renal interstitial damage scores[(57.30±6.80)points,(51.60±6.30)points vs.(27.20±3.60)points]in the severe and moderate groups were significantly higher than those in the mild group(all P<0.01).The expression level of miR-151a-3p in LN children was negatively correlated with the SLEDAI score and renal interstitial damage score(r=-0.682,-0.627,all P<0.001).Conclusions The expression level of miR-151a-3p in PBMCs of LN children is significantly decreased.The declined miR-151a-3p level is closely related to disease activity and vascular damage,and may be involved in the occurrence and development of LN.