支气管哮喘患儿lncRNA PVT1和炎症因子表达与激素治疗敏感性的关系研究

Relationship between lncRNA PVT1 and inflammatory factors and sensitivity to hormone therapy in children with bronchial asthma

目的分析长链非编码RNA中浆细胞瘤多样性异位基因1(lncRNA PVT1)、炎症因子与支气管哮喘患儿激素治疗敏感性的关系。方法选取2019年1月-2019年12月张家口市第一医院收治的60例支气管哮喘患儿作为研究对象,根据不同的激素治疗敏感性分为敏感组和抵抗组,各30例。采集两组患儿气管平滑肌细胞进行原代培养,使用RT-PCR检测lncRNA PVT1相对表达量,ELISA法检测血清炎症因子及siRNA沉默lncRNA PVT1前后原代培养细胞的炎症因子表达水平。结果抵抗组血清及原代培养细胞lncRNA PVT1较敏感组高(P<0.05)。抵抗组血清IL-1β、IL-6、IL-10及TNF-α表达水平较敏感组高(P<0.05)。抵抗组沉默前后原代培养细胞中IL-1β、IL-6、IL-10及TNF-α表达水平的差值较敏感组高(P<0.05)。lncRNA PVT1[OlR=0.145(95% CI:0.057,0.762),P=0.029]、IL-10[OlR=2.853(95% CI:1.542,5.969),P=0.017]及TNF-α[OlR=4.482(95% CI:1.404,13.858),P=0.031]为支气管哮喘患儿激素治疗敏感性的影响因素(P<0.05)。血清lncRNA PVT1、IL-10与TNF-α联合预测支气管哮喘患儿发生激素治疗抵抗的敏感性为91.25%(95% CI:0.835,0.986),特异性为88.74%(95% CI:0.810,0.965),AUC为0.955(95% CI:0.903,1.000),且较单独指标预测的AUC高(P<0.05)。结论过表达lncRNA PVT1可明显加剧支气管哮喘患儿的气道炎症反应,进而降低气管平滑肌对激素治疗的敏感性。

Objective To analyze the relationship between long-chain non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and inflammatory factors and sensitivity to hormone therapy in children with bronchial asthma.Methods A prospective controlled study was conducted,with 60 bronchial asthma children treated in our hospital from January to December 2019 being selected and divided into hormone-sensitive group (30 cases) and hormone-resistant group (30 cases).The tracheal smooth muscle cells collected from all the children were primarily cultured.Polymerase chain reaction (PCR) was used to detect the expression level of lncRNA PVT1,and enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of inflammatory factors in primarily cultured cells before and after silencing lncRNA PVT1 via siRNA.Results The expression levels of lncRNA PVT1 in serum and primarily cultured cells of hormone-resistant group were higher than those of hormone-sensitive group (P<0.05).Serum levels of IL-1β,IL-6,IL-10 and TNF-α in the hormone-resistant group were higher than those in the hormone-sensitive group (P<0.05).The differences in the expression levels of IL-1β,IL-6,IL-10 and TNF-α in the primarily cultured cells before and after silencing of lncRNA PVT1 in the hormone-resistant group were greater than those in the hormone-sensitive group (P<0.05).After multiple stepwise regression analysis,lncRNA PVT1,IL-10,and TNF-α levels were found to be the influencing factors of the sensitivity to hormone therapy in children with bronchial asthma (P<0.05).The receiver operating characteristic (ROC) analysis showed that the sensitivity of serum lncRNA PVT1,IL-10 and TNF-α to predict resistance to hormone therapy in children with bronchial asthma was 91.25%,specificity was 88.74%,and area under the ROC curve (AUC) was 0.955,which was significantly higher than the AUC of a single index (P<0.05).Conclusions The lncRNA PVT1 and inflammatory factors are both associated with the sensitivity to hormone therapy in children with bronchial asthma,and the combined prediction of hormone resistance in children is effective,which may be related to the fact that silencing lncRNA PVT1 can inhibit inflammatory response and therefore improve the sensitivity to hormone therapy.