高-低氧双向诱导制备新生大鼠支气管肺发育不良并发肺动脉高压模型  

A novel neonatal rat model of bronchopulmonary dysplasia complicated by pulmonary hypertension established by high-low oxygen bidirectional induction

作　　者：邢玉娇 衣曼 富建华[1] 薛辛东[1] XING Yujiao;YI Man;FU Jianhua;XUE Xindong(Department of Pediatrics,Shengjing Hospital,China Medical University,Shenyang 110004,China;Department of Pathology,Children’s Hospital Research Insititute of Manitoba,University of Manitoba,Winnipeg,R3E 3P4,Canada)

机构地区：[1]中国医科大学附属盛京医院儿内科,沈阳110004 [2]加拿大曼尼托巴大学儿童医院研究所生理系,Winnipeg R3E 3P4

出　　处：《中国医科大学学报》2020年第9期846-853,共8页Journal of China Medical University

摘　　要：目的通过高-低氧双向诱导方法,建立新生大鼠支气管肺发育不良(BPD)并发肺动脉高压(PH)模型。方法将足月新生SD大鼠随机分为4组,A组(21%O2)、H组(60%O2)、AL组(13%O2)和HL组(60%~13%O2),分别于生后7 d和14 d进行超声心动图检查,计算右心室射血时间/肺动脉加速时间(RVET/PAAT)比值;于生后14 d进行肺功能测定;留取肺组织及心脏标本,测定右心室湿质量/(左心室+室间隔湿质量)比值;对肺组织切片进行HE染色,α-平滑肌肌动蛋白(α-SMA)免疫组织化学染色和弹性蛋白染色并评估。结果生后14 d HL组RVET/PAAT比值较A组明显升高;肺功能测定结果显示,HL组组织阻力及弹性阻力显著升高;肺组织切片可见肺泡化进程受阻;α-SMA,Elastin表达及分布均发生改变。结论应用60%~13%高-低氧双向诱导方法建立的大鼠模型,不仅符合经典BPD病理表现,同时形成了PH,与传统BPD模型相比,更适合临床早产儿BPD并发PH的相关研究。Objective This study aimed to establish a neonatal rat model of bronchopulmonary dysplasia(BPD)complicated by pulmonary hypertension(PH)high-low oxygen bidirectional induction.Methods Full-term S-D rats were randomly divided into four groups:group A(21%O2),group H(60%O2),group AL(13%O2),and group HL(60%-13%O2).Echocardiography was performed on day 7 and 14 after birth,and RVET/PAAT ratios were calculated.Lung function was evaluated on day 14 after birth.Lung and heart tissues were collected,and the ratios of the right ventricular wet weight/(left ventricular+interventricular wet weight)were calculated.HE staining,alpha-SMA immunohistochemical staining,and Elastin specific staining were performed on lung sections to evaluate lung development.Results the RVET/PAAT ratio in the HL group was significantly higher than that in the A group on day 14 after birth.On lung function evaluation,tissue resistance and elastic resistance were significantly increased in the HL group.Arrested alveolarization and altered distribution of alpha-SMA and Elastin were observed on lung section staining.Conclusion The animal model established by the 60%to 13%(high-low)oxygen bidirectional induction method was consistent with the pathological changes in the classic model of BPD,and pulmonary hypertension was induced at the same time as the heart ultrasonic and lung function verification.The new BPD-PH model may be more suitable for premature BPD-PH research than the classical BPD model.

关 键 词：高氧-低氧 支气管肺发育不良 肺动脉高压 大鼠 早产儿 

分 类 号：R722.6[医药卫生—儿科]