miR-4433b-5p及SP-A在老年COPD患者病情严重程度及频繁加重风险中的价值  

The value of miR-4433b-5p and SP-A in severity and frequent exacerbations risk in elderly patients with COPD

作　　者：石雪峰[1] 何响 孙泽蕊 王建祥 解友邦[1] 多杰[1] SHI Xue-Feng;HE Xiang;SUN Ze-Rui(Qinghai Provincial People′s Hospital,Xining 810001,Qinghai,China)

机构地区：[1]青海省人民医院,青海西宁810001 [2]青海大学

出　　处：《中国老年学杂志》2023年第15期3658-3664,共7页Chinese Journal of Gerontology

基　　金：青海省自然科学基金(2017-ZJ-954Q);青海省人民医院院内指导课题(2018-004);青海省卫生计生系统重点课题(2017-wjzd-10)。

摘　　要：目的分析青海地区老年慢性阻塞性肺疾病(COPD)患者血浆miR-4433b-5p、基质金属蛋白酶(MMP)-2及肺泡表面活性蛋白(SP)-A表达水平变化及其临床意义。方法随机选取出院后定期随访的60岁以上COPD患者和健康体检者作为COPD组及对照组。所有受试者采集清晨空腹静脉血留取血浆。选择5例对照组及COPD组患者进行高通量测序。选择两组各35例为对照验证组和COPD验证组,收集血浆提取RNA后用qRT-聚合酶链反应(PCR)检测miR-4433b-5p表达,用酶联免疫吸附试验(ELISA)检测血浆中MMP-2及SP-A的浓度,完善肺功能检查并进行为期1年的随访。结果以P值≤0.05且差异倍数(FC)≥2为判断标准,共筛选出老年COPD患者差异表达的miRNAs 159个,其中上调53个,下调106个,差异表达miRNAs靶基因信号通路主要富集于神经生长因子(NGF)等信号通路;与对照验证组相比,COPD验证组血浆MMP-2及SP-A浓度明显升高(P<0.05);血浆miR-4433b-5p与第1秒用力呼力量占预计值百分比(FEV1%)预计值呈显著正相关(r=0.429,P<0.05),而与1年急性加重次数呈显著负相关(r=-0.455,P<0.05);血浆MMP-2及SP-A与FEV1%预计值呈显著负相关(r=-0.462、-0.422,P<0.01、P<0.05),与1年急性加重次数呈显著正相关(r=-0.422、0.429,均P<0.05);二元Logistic回归分析显示,血浆miR-4433b-5p及SP-A可作为老年COPD频繁加重风险评估指标;受试者工作特征(ROC)曲线下面积(AUC)结果显示血浆miR-4433b-5p及SP-A联合预测AUC、灵敏度分别为0.866、82.6%,在预测老年COPD频繁加重风险评估中优于单标志物。结论老年COPD血浆中miR-4433b-5p表达降低,血浆miR-4433b-5p及SP-A可作为老年COPD患者严重程度评估及未来急性加重风险的危险因素。miR-4433b-5p可能通过调控MMP-2调控COPD病理学过程。Objective To analyze the change of expression levels of miR-4433b-5p,matrix metalloproteinase(MMP)-2 and alveolar surfactant protein(SP)-A in elderly patients with chronic obstructive pulmonary disease(COPD)in Qinghai area and their clinical significance.Methods COPD patients who were regularly followed up after discharge and healthy subjects older than 60 years old were randomly selected as COPD group and control group.Fasting venous blood was collected from all subjects in the morning to collect plasma.Five samples from control and COPD groups were selected for high-throughput sequencing.Two groups with 35 cases each were selected as control verification group and COPD verification group,the expression of miR-4433b-5p was detected by qRT-polymerase chain reaction(PCR)after RNA extraction from plasma,the plasma concentrations of MMP-2 and SP-A were detected by enzyme-linked immunosorbent assay(ELISA),pulmonary function tests were completed and 1-year follow-up was performed.Results A total of 159 differentially expressed miRNAs in elderly COPD patients were screened with P<0.05 and fold change(FC)≥2 as the criteria,of which 53 were up-regulated and 106 were down-regulated.The signaling pathways of differentially expressed miRNAs target genes were mainly concentrated in nerve growth factor(NGF)and other signaling pathways.Compared with the control verification group,the plasma concentrations of MMP-2 and SP-A in COPD verification group were significantly increased(P<0.05);plasma miR-4433b-5p was significantly positively correlated with the predicted percentage of forced expiratory volume in the first second(FEV1%)(r=0.429,P<0.05),negatively and significantly correlated with the number of acute exacerbation within one year(r=-0.455,P<0.05);plasma MMP-2 and SP-A were negatively and significantly correlated with predicted FEV1%(r=-0.462,-0.422,P<0.01,P<0.05),positively and significantly correlated with the number of acute exacerbation within one year(r=-0.422,0.429,all P<0.05).Binary Logistic regression results sh

关 键 词：慢性阻塞性肺疾病 miRNA-4433b-5p 基质金属蛋白酶(MMP)-2 肺泡表面活性蛋白(SP)-A 

分 类 号：R563[医药卫生—呼吸系统]