沉默lncRNA MEG3对慢性阻塞性肺疾病小鼠肺功能的改善作用及其机制  

Improvement of silencing LNCRNA MEG3 on lung function of COPD mice and its mechanism

作　　者：叶婷[1] 余维巍[2] 张存泰[2] YE Ting;YU Weiwei;ZHANG Cuntai(Department of Clinical Nutrition,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China;不详)

机构地区：[1]华中科技大学同济医学院附属同济医院临床营养科,武汉430030 [2]华中科技大学同济医学院附属同济医院老年医学科

出　　处：《山东医药》2022年第35期40-43,共4页Shandong Medical Journal

基　　金：国家自然科学基金青年基金资助项目(81500032)。

摘　　要：目的观察沉默lncRNA MEG3对慢性阻塞性肺疾病(COPD)小鼠肺功能的改善作用,并探讨其机制是否与调控白细胞介素1β(IL-1β)有关。方法将32只野生型C57BL/6J小鼠随机分成control组、COPD组、COPD+NC组、COPD+siMEG3组,每组8只;除control组小鼠外,均采用香烟烟雾烟熏的方法建立COPD模型,COPD+NC组、COPD+siMEG3组同时尾静脉注射siRNA-Lipofectamine、NC-Lipofectamine复合体2.5 mg/kg,control组、COPD组注射等量生理盐水,1次/周,共注射12次。ASPER数据库及染色质免疫共沉淀实验证实lncRNA MEG3与IL-1β启动子区域存在结合位点,二者存在靶控关系。比较各组小鼠肺组织病理改变、氧合指数及肺湿重/干重,肺组织及BALF中的lncRNA MEG3及IL-1βmRNA、蛋白表达。结果control组小鼠肺组织结构正常;COPD组及COPD+NC组小鼠肺泡结构紊乱,部分肺泡可见不规则扩大,肺泡、小气道及肺血管可见大量炎症细胞浸润;COPD+siMEG3组小鼠肺泡结构较COPD组及COPD+NC组完整,肺泡、小气道和肺血管少量炎症细胞浸润,支气管平滑肌层及管壁结构偶见异常。与control组和COPD+siMEG3组比较,COPD组、COPD+NC组肺湿重/干重均升高,氧合指数均降低(P均<0.05)。各组小鼠BALF中均未检测到lncRNA MEG3表达。与control组、COPD+siMEG3组比较,COPD组及COPD+NC组肺组织lncRNA MEG3表达均升高且肺组织、BALF中IL-1βmRNA、蛋白均升高(P均<0.05)。结论沉默lncRNA MEG3可通过降低IL-1β表达而减轻COPD小鼠的肺损伤,从而发挥肺保护作用。Objective To observe the improvement effect of silencing lnc RNA MEG3 on lung function in mice with chronic obstructive pulmonary disease(COPD),and to investigate whether its mechanism is related to the interleukin-1β(IL-1β).Methods Thirty-two wild-type(WT)C57BL/6J mice were randomly assigned into four groups:control group,COPD group,COPD+NC group,and COPD+si MEG3 group,with eight mice in each group.All mice were exposed to cigarette smoke(CS)except the mice in the control group.The COPD+NC group and COPD+si MEG3 group were injected with si RNA lipofectamine or NC lipofectamine complex(2.5 mg/kg via tail vein injection,once a week,12 times in total),and the control group and COPD group were injected with the same amount of saline at the same time.Here we confirmed that there were binding sites between lnc RNA MEG3 and the promoter region of IL-1βthrough ASPER database and chromatin immunoprecipitation experiment,thus there was a regulatory relationship between lnc RNA MEG3 and IL-1β.We further compared the pathological changes,oxygenation index,lung wet weight/dry weight,the m RNA and protein expression levels of lnc RNA MEG3 and IL-1βin the lung tissues and BALF of mice in each group.Results We observed that the structure of lung tissue in the control group was normal.In the COPD group and COPD+NC group,the structure of pulmonary alveoli was disordered and enlarged partly and irregularly,in addition,a large number of inflammatory cells were infiltrated in the alveoli,small airways and pulmonary vessels.Compared with the COPD group and COPD+NC group,the alveolar structure of mice in the COPD+si MEG3 group was more complete with a few inflammatory cells infiltration,and the bronchial smooth muscle layer and tube wall structure were occasionally abnormal.Compared with the control group and COPD+si MEG3 group,the mice of COPD group and COPD+NC group showed higher ratio of lung wet weight/dry weight,and lower oxygenation index(all P<0.05).The expression of lnc RNA MEG3 was not detected in BALF of mice in all gro

关 键 词：lncRNA MEG3 白细胞介素1Β 氧合指数 慢性阻塞性肺疾病 

分 类 号：R563.4[医药卫生—呼吸系统]