高氧致新生鼠慢性肺疾病中PDZ结合基序转录共激活因子的表达及其意义  

Expression and significance of transcriptional co-activator with PDZ-binding motif in neonatal rat with chronic lung disease induced by hyperoxia

作　　者：贾献献 范林 吴波[1] 黄金辉 许巍[1] Jia Xianxian;Fan Lin;Wu Bo;Huang Jinhui;Xu Wei(Department of Pediatrics,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院儿内科,沈阳110004

出　　处：《中国小儿急救医学》2020年第7期521-526,共6页Chinese Pediatric Emergency Medicine

基　　金：国家自然科学基金(81771621,81270726);辽宁省自然科学基金(20170541023);辽宁省重点研发指导计划(2019JH8/10300023)。

摘　　要：目的探讨高氧致新生大鼠慢性肺损伤中PDZ结合基序转录共激活因子(transcriptional co-activator with PDZ-binding motif,TAZ)的表达及其作用。方法建立新生大鼠高氧致肺损伤模型,实验组和对照组分别吸入氧气(85%)和空气。分别在第1、3、7、14、21天留取肺组织,肺组织切片苏木精-伊红染色观察肺组织病理改变,应用实时荧光定量聚合酶链式反应、Western blot和免疫组织化学技术检测肺组织中TAZ、表面活性蛋白C(surfactant protein C,SPC)、水通道蛋白5(aquaporin-5,AQP5)蛋白的动态表达情况。结果实验组肺组织逐渐出现肺泡间隔增厚,肺泡棘消失,肺泡腔增大,数目减少,肺泡结构简单化。与对照组相比,实验组肺组织中第1、3天TAZ、SPC、AQP5表达无差异(P>0.05);第7、14、21天实验组肺组织中TAZ的mRNA和蛋白表达明显降低,SPC的mRNA和蛋白表达明显升高,而AQP5的mRNA和蛋白表达量下降,差异均有统计学意义(P<0.05)。结论高氧可致新生大鼠肺泡结构紊乱和肺发育停滞;由SPC、AQP5表达结果说明Ⅰ型肺泡上皮细胞损伤严重,Ⅱ型肺泡上皮细胞虽然数量有所增加但其分化能力明显下降,而TAZ表达量减少可能致使大量的Ⅱ型肺泡上皮细胞失去了分化为Ⅰ型肺泡上皮细胞的功能。Objective To investigate expression level of transcriptional co-activator with PDZ-binding motif(TAZ)in neonatal rats with chronic lung diseases induced by hyperoxia and explore its potential role in the disease.Methods The model of high-oxygen-induced lung injury in neonatal rats was established by continuous inhalation of high-concentration oxygen.The rats in experimental group inhaled 85%oxygen,while the rats in control group inhaled air.The lung tissues were collected at the 1st,3rd,7th,14th and 21st day,and the lung tissue sections were stained with hematoxylin and eosin staining to observe the pathological changes of the lung.In addition,the dynamic expressions of TAZ,surfactant protein C(SPC)and aquaporin-5(AQP5)in lung tissue were detected by real-time PCR,western blot and immunohistochemistry staining.Results In the experimental group,with the prolongation of oxygen inhalation time,we found that the alveolar cavity increased,the number decreased,the alveolar septum thickened,and the alveolar structure was simplified.Compared with the control group,there was no difference in TAZ,SPC and AQP5 expression at 1st and 3rd days in the lung tissue in the experimental group(P>0.05).However,at 7,14 and 21 days,the expression of TAZ in mRNA and protein level in lung tissue in experimental group decreased significantly,and the expression of SPC in mRNA and protein level increased significantly,while the expression of AQP5 in mRNA and protein level decreased,the differences were all statistically significant(P<0.05).Conclusion Hyperoxia can cause alveolar structure disorder and pulmonary arrested development in neonatal rat.The expression levels of SPC and AQP5 show that the injury of typeⅠalveolar epithelial cells(AECⅠ)is severe.Although the number of typeⅡalveolar epithelial cells(AECⅡ)increased,but its differentiation capacity decreased obviously.The decrease of TAZ expression may cause AECⅡlose the function of differentiation into AECⅠ.

关 键 词：PDZ结合基序转录共激活因子 分化 Ⅰ型肺泡上皮细胞 Ⅱ型肺泡上皮细胞 慢性肺损伤 

分 类 号：R722.1[医药卫生—儿科]