摘要
目的研究人附睾蛋白4(HE4)在慢性阻塞性肺疾病(COPD)中的表达水平,从而为C O PD寻找新的生物学标志物.方法纳入因肺部疾病接受手术治疗的患者12例,根据获得的肺组织患者的第一秒用力呼气容积/用力肺活量参数分为对照组6例和C O PD组6例,免疫组织化学检测人肺组织内H E4的分布及表达.动物模型中,采用随机数字表法将24只6周C57BL/6雄性小鼠随机分为对照组和COPD组,每组12只.COPD组暴露于3 ppm的臭氧,每周2次,每次3 h;对照组在相同条件下暴露于空气,于1周、3周末次暴露24 h后每组分别处死6只小鼠,采用酶联免疫吸附试验检测臭氧模型小鼠支气管肺泡灌洗液中H E4的表达水平;以1%、2.5%、5%浓度的香烟烟雾提取物预处理人支气管上皮细胞24 h后,采用实时定量逆转录聚合酶链式反应检测HE4 mRNA的表达水平.结果 COPD患者肺组织支气管上皮细胞中H E4表达水平较对照组降低(t=2.267,P<0.05).在1周及3周时,小鼠支气管肺泡灌洗液中HE4表达水平均低于对照组(t=2.423、2.987,P值均<0.05).HE4 mRNA在2.5%、5%香烟烟雾提取物预处理人支气管上皮细胞中表达水平均低于对照组(t=3.895、4.060,P值均<0.05).结论 HE4在COPD支气管上皮细胞中表达水平降低,表明HE4可能参与COPD的发生、发展过程,是COPD潜在的生物学标记物.
Objective To study the expression level of human epididymis protein 4 ( HE4) in chronic obstructive pulmonary disease ( COPD) ,so as to find a new biological marker for COPD . Methods According to the obtained parameters of forced expiratory volume in the first second/forced vital capacity ,12 patients who received surgical treatment for lung diseases were included and divided into the control group ( 6 cases) and the COPD group ( 6 cases) .The distribution and expression of HE4 in human lung tissues were detected by immunohistochemistry .In the animal model ,24 male C57BL/6 mice at 6 weeks were randomly divided into control group and COPD group by random number table method ,12 mice in each group .The COPD group was exposed to ozone at 3 ppm twice a week for 3 hours each time ,and the control group was exposed to air under the same conditions .1 week and 3 weeks later ,6 mice were killed 24 hours after the last exposure in each group . Enzyme-linked immunosorbent assay was used to detect HE4 expression in bronchoalveolar lavage fluid in mice .In cell experiments ,human bronchial epithelial cells were pretreated with 1% ,2 .5% ,and 5% concentrations of cigarette smoke extract for 24 hours ,and the expression level of HE4 mRNA was detected by real-time quantitative reverse transcript-polymerase chain reaction .Results There was less HE4 expression in bronchial epithelial cells of COPD group than the control group ( t =2 .267 , P <0 .05) .After 1 and 3 weeks ,the HE4 expression levels in bronchoalveolar lavage fluid of ozone model mice were less than the control group ( t = 2 .423 , 2 .987 ,both P <0 .05) .After pretreatment with 2 .5% ,5% cigarette smoke extract ,the expression levels of HE4 mRNA in human bronchial epithelial cells were less than the control group ( t =3 .895 ,4 .060 ,both P < 0 .05 ) .Conclusions The decreased expression level of HE4 in COPD bronchial epithelial cells indicates that HE4 may be involved in the occurrence and development of COPD and it may be a potential biomarker of COPD .
作者
朱筱慧
贾嫚
许家艳
孟亚奇
乔莹莹
姚欣
Zhu Xiaohui;Jia Man;Xu Jiayan;Meng Yaqi;Qiao Yingying;Yao Xin(Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital ofNanjing Medical University, Nanjing 210029, China;Department of Respiratory Medicine, theThird Affiliated Hospital of Suzhou University, Changzhou 213003, China)
出处
《国际呼吸杂志》
2019年第18期1391-1396,共6页
International Journal of Respiration
关键词
肺疾病
慢性阻塞性
人附睾蛋白4
Pulm onary disease, chronic obstructive
Hum an epididymis protein 4