先天性膈疝肺动脉高压的实验研究  

Experimental Study in Pulmonary Hypertension of Congenital Diaphragmatic Hernia

作　　者：余家康[1] 何秋明[1] 肖尚杰[2] 钟微[1] 夏慧敏[1] 

机构地区：[1]广州医学院附属广州市儿童医院外科,510120 [2]广州医学院附属广东省妇儿医院,510010

出　　处：《临床小儿外科杂志》2009年第1期25-30,共6页Journal of Clinical Pediatric Surgery

基　　金：本研究为广东省面上项目（粤卫2007第97号）

摘　　要：目的研究先天性膈疝（Congenital diaphragmatic hernia，CDH）肺发育不良中肺动脉高压（Dulmonary hypertension，PH）的量化指标，探讨血管内皮生长因子（vascular endothelial growth factor，VEGF）在CDH胎肺中的表达及在CDH肺动脉高压发生中的可能作用，探讨地塞米松（Dexamethasone，Dex）对VEGF和CDH肺发育的影响。方法采用Nitrofen诱导CDH模型胎鼠并分组：Dex组予以产前Dex治疗，CDH组未给予Dex，另取正常胎鼠为对照组。采用组织学测量、肺蛋白含量检测等方法，测定出平均肺泡面积、平均肺泡间隔厚度、每高倍视野肺血管数、动脉中膜厚度占外径比（MT％）、管壁面积占血管总面积比（WA％）、管腔面积占血管总面积比（LA％）、左肺与体重比、左肺蛋白含量与体重比等；实时荧光定量PCR（QPCR）和免疫蛋白印迹（Western blotting）方法检测各组胎肺中VEGF的表达及相对含量。结果与对照组相比，CDH组胎肺显著发育不良，包括肺微小动脉结构明显异常，表现为每高倍视野肺血管数减少、MT％增大、WA％增大，LA％减小（均P〈0．05）；另外VEGFmRNA及蛋白水平均明显升高（P〈0．05）。与CDH组相比，Dex组胎肺发育明显改善，表现为每高倍视野肺血管数增加、动脉中膜厚度占外径比减小、管腔面积占血管总面积比增大（均P〈0．05）；但VEGF mRNA及蛋白水平未发现明显变化（P〉0．05）。结论VEGF在CDH胎肺中的表达增高可能是CDH肺发育不良形成机制之一；产前地塞米松治疗可明显改善肺微小动脉结构异常及肺发育不良，但未发现对VEGF的表达有影响，提示Dex可能并非通过调节VEGF的表达而发挥改善肺动脉高压及肺发育不良的作用。Objective To investigate the value of pulmonary hypertension in hypoplastic lung of congenital diaphragmatic hernia,VEGF expression feature in lungs of CDH and its role plays in formation of pulmonary hypertension of CDH,the regulation of VEGF by prenatal dexamethasone in CDH fetal lungs. Methods Time-mated female SD rats were randomly divided into three groups： control group, Nitrofen-induced CDH group, and Dex-treated group. Average area of alveoli, average of thickness of the alveolar walls, number of artery in each high power （HP）, percentages of intimae-media thickness to the external diameter （MT%）, wall area to total transeetional area （WA%） and luminal area to total transectional area （LA%）,left lung weight to fetal weight ratio, lef! lung protein to fetal weight ratio were calculated as evaluating the pulmonary devolpment. Expression level of VEGF mRNA and protein in each group was detecting by the real-time Quantitative PCR and Western blotting. Results Compared to control group ,pulmonary lungs including structural abnormality of artery in CDH groups were shown by reduced number of artery in each high power,increased MT% ,decreased LA% ,and the VEGF levels significantly higher. Compared to CDH group,pulmonary lungs in CDH groups were significantly improved ,which shown by increased number of artery in each high power,decreased MT% , increased LA%, and no significant change of the VEGF levels. Conclusions Pulmonary hypertension in CDH lungs could be evaluated by number of artery in HP, MT% , LA% ,etc. It is hypothesized that pulmonary hypopla.~ia and hypertension in CDH may be caused by increased expression level of VEGF. Dex could promot the maturity of CDH and normalize strnctural abnormality of artery which may be not related to regulate the expression of VEGF.

关 键 词：疝 横膈/先天胜 高血压 肺性 

分 类 号：R543.2[医药卫生—心血管疾病] R726.556[医药卫生—内科学]