慢性肺疾病早产鼠的肺组织中HoxB5 mRNA表达及其对肺发育的影响  

Expression of HoxB5 mRNA and their effect on lung development in premature rats with hyperoxiainduced chronic lung disease

作　　者：富建华[1] 薛辛东[1] 潘丽[1] 许巍[1] 

机构地区：[1]中国医科大学附属第二医院儿科,沈阳110004

出　　处：《中华儿科杂志》2008年第7期540-543,共4页Chinese Journal of Pediatrics

基　　金：国家自然科学基金资助项目（30440056）

摘　　要：目的探讨高氧致慢性肺疾病（CLD）早产鼠的肺组织HoxB5基因表达规律及其对肺发育抑制的影响机制。方法将孕21d剖宫取出的新生鼠（即早产鼠）80只随机分为实验组及对照组（每组均为40只），采用高浓度氧诱导早产鼠CLD模型，分别于实验后1、3、7、14、21d采集肺组织，应用反转录聚合酶链反应（RT-PCR）等技术，测定肺组织HoxB5、AQP-5、SP-B mRNA水平，并同期观察肺发育的评价指标放射状肺泡计数（RAC）的变化。结果生后1d和3d，实验组和对照组的HoxB5、AQP-5及SP-B mRNA水平和RAC均差异无统计学意义（P〉0．05）；生后7d，与对照组比较，实验组RAC开始减少（6．35±0．83 vs．7．57±0．52），HoxB5（0．98±0．14 vs．1．20±0．16）及AQP-5（0．78±0．11 vs．1．04±0．19）mRNA也明显降低（P〈0．05）、SP-B（1．34±0．04 vs.1．04±0．11）反而明显升高（P〈0．05）；生后14d，实验组RAC逐渐减少，HoxB5及AQP-5 mRNA持续下降，21d，HoxB5（0．64±0．11 vs．1．18±0．13）及AQP-5（0．67±0．12 vs．0．97±0．01）mRNA降至最低（P〈0．01），而SP-B（1．43±0．07 vs．1．12±0．09）mRNA升至最高（P〈0．01）；实验组肺组织HoxB5 mRNA水平及RAC呈明显正相关（γ=0．585，P〈0．01）。结论暴露高氧中早产鼠的肺组织HoxB5基因呈低水平表达，其表达降低可能导致的Ⅱ型肺泡上皮细胞向Ⅰ型肺泡上皮细胞的分化障碍与CLD肺发育停滞密切相关。Objective Resolution of alveolar damage after lung injury requires finely orchestrated processes that include coordinated and effective tissue reconstruction to reestablish a functional barrier. Reconstitution of denuded type Ⅰ alveolar epithelial cell that undergo apoptotic and necrotic death after lung injury is required in many pulmonary diseases. Disruption of distal airway development and type Ⅱ - type Ⅰ alveolar epithelial cell differentiation after lung injury and disordered repair of the alveolus after injury is one of the predominant pathological characteristics of chronic lung disease （CLD） of premature infants. HoxB5 belongs to the Hox gene family encoding transcription factors known for their role in skeletal patterning and the elaboration of organs. HoxB5 is required for embryonic respiratory tract morphogenesis. The present study aimed to test the hypothesis that HoxB5 may participate in the etiology of CLD and to understand possible mechanism. Methods Premature rat pups were taken out surgically at gestational age 21 d. CLD was induced by hypemxia exposure in neonatal premature rats. Eighty premature rats were randomly exposed to hypemxia （FiO2 =0.90, CLD group） and to room air （FiO2 =0.21, control group） （n =40 each）. Lung specimens were obtained respectively on days 1, 3, 7, 14 and 21 after exposure. Histopathologic changes was assayed after hematoxylin and eosin （HE） staining and pulmonary development was evaluated by lung coefficient and radical alveolar counts （ RAC ）, dynamic changes of RAC were observed ; and the expression of HoxBS, AQP-5, and SP-B mRNA were assayed by reverse transcription polymerase chain reaction （RT-PCR）. Results There were no significant differences in the RAC and the expression level of HoxBS, AQP-5, and SP-B mRNA between the CLD and the control groups within 3 days after birth （P 〉 0. 05 ）. However, compared to the control group, the RAC of the CLD group was reduced （6. 35 ±0. 83 vs. 7.67 ± 0. 52）, and the expression of H

关 键 词：肺疾病 早产 高氧 基因 大鼠 

分 类 号：R686[医药卫生—骨科学]