特发性肺纤维化患者血清外泌体microRNA表达谱的变化及临床意义

Changes and clinical significance of serum exosomal microRNA expression in patients with idiopathic pulmonary fibrosis

目的探讨特发性肺纤维化(IPF)患者血清外泌体microRNA表达谱的变化及其临床意义。方法选择2019年1月至2021年1月就诊于新乡医学院第一附属医院的24例初诊IPF患者作为IPF组,另选择24名年龄、性别与IPF组匹配的健康体检者为对照组。应用肺功能检测仪检测2组受试者肺总量(TLC)、第1秒用力呼气容积占预计值百分比(FEV_(1)%pred)、一氧化碳弥散量占预计值百分比(DLCO%pred)等肺功能指标。分离提取2组受试者血清外泌体进行microRNA高通量测序。分析IPF患者外泌体microRNA表达谱变化及其与肺功能的相关性。结果IPF组患者的TLC、FEV_(1)%pred、DLCO%pred均显著低于对照组(P<0.05)。2组受试者间共有168种差异表达的microRNA,其中3种microRNA(miR-1-3p、miR-99a-5p、miR-411-5p)涉及磷脂酰肌醇激酶/丝氨酸/苏氨酸激酶/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路且与IPF患者DLCO%pred呈正相关(r=0.575、0.617、0.825,P<0.05)。结论IPF患者血清外泌体microRNA表达谱与健康人群相比发生变化,异常表达的外泌体microRNA可能通过活化PI3K/Akt/mTOR信号通路参与IPF的发生。

Objective To investigate the changes of serum exosomes microRNAs expression in patients with idiopathic pulmonary fibrosis(IPF)and its clinical significance.Methods Twenty-four preliminary diagnosis of IPF patients admitted to the First Affiliated Hospital of Xinxiang Medical University from January 2019 to January 2021 were selected as the IPF group,and 24 healthy physical examiners matched with the IPF group in the age and sexual were selected as the control group.The total lung capacity(TLC),the forced expiratory volume in one second/predict value(FEV_(1)%pred)and the carbon mon-oxide diffusing capacity/predict value(DLCO%pred)of subjects in the two groups were measured by pulmonary function tester.Serum exosomes of subjects in the two groups were isolated and extracted for microRNAs high-throughput sequencing.The changes of microRNAs expression in exosomes of IPD patients and its correlation with lung function were analyzed.Results The TLC,FEV_(1)%pred and DLCO%pred of patients in the IPF group were lower than those in the control group(P<0.05).There were 168 differentially expressed microRNAs in exosomes of subjects between the two groups.Among them,three microRNAs(miR-1-3p,miR-99a-5p,and miR-411-5p)involved in phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway,and the three microRNAs were positively correlated with DLCO%pred(r=0.575,0.617,0.825;P<0.05).Conclusion Compared with the health people,the expression of microRNAs in serum exosomes of IPF patients is changed.The abnormally expressed microRNAs in exosomes may be involved in the occurrence of IPF by activating PI3K/Akt/mTOR signaling pathway.