Pulmonary Expression of Adrenomedullin in a Rat Model of Congenital Diaphragmatic Hernia

背景/目的：尽管近年来治疗取得了一定进展，但先天性腹股沟疝（CDII）合并肺发育不良的预后仍较差，胎儿和新生儿时期的肺发育被认为是更重要的。肾上腺髓质素（AM）是一种新的血管舒张肽，也被发现在胎肺分化和成熟的机制中发挥作用。在这项研究中，我们研究了肾上腺髓质素在大鼠模型的CDH肺表达。研究方法：在孕9.5天的SD大鼠中，给予400 mg/kg的除草醚橄榄油溶液后，在定时妊娠的SD大鼠（期限：22天）中诱导先天性膈疝，并在第16、19和21天收获胎肺。在对照组动物中，给予相同剂量的橄榄油，但不含除草醚。测定除草醚组和对照组大鼠的肺/体重比和肺AM。结果如下：与对照组（1.63+/-0.30，4.16 +/-0.45，2.55 +/-0.26）相比，除草醚组的肺/体重比（%）显著降低（妊娠16天为1.24+/-0.13，19天为3.03+/-0.25，21天为1.85+/-0.26）。肺AM在妊娠第19天和第21天，除草醚组的fmol/mg湿组织（妊娠第19天为4.51 ± 0.78，妊娠第21天为4.95 ± 1.95）：与对照组比较（1.35 ± 0.36，3.2 ± 1.17），而在妊娠第16天无显著性差异（0.44 ± 0.10vs0.46 ± 0.13）。结论：妊娠晚期CDH大鼠模型肺组织中肾上腺髓质素表达增加，提示AM可能是肺组织的生长因子之一。

Background/Purpose: While the prognosis in congenital diaphragmatic hernia (CDII) with hypoplastic lung is still poor in spite of recent progress of the therapy, lung growth in the period of fetus and newborn has been thought to be more important. Adrenomedullin (AM), a novel vasodilating peptide, has also been found to play a role in the mechanisms of fetal lung differentiation and maturation. In this study, we examined pulmonary expression of adrenomedullin in a rat model of CDH. Methods: Congenital diaphmgmatic hernia was induced in timed-pregnant SD rats (term:22 days) after administration of 400 mg/kg of nitrofen in olive oil on day 9.5 of gestation and fetal lungs were harvested on day 16, 19, and2l. In control animals, the same doze of olive oil was given without nitrofen. Lung-to-body weight ratio and pulmonary AM were measured in nitrofen group and control group. Results: Lung-to-body weight ratio (%)was significantly lower in nitrofen group (1.24+/-0.13 at gestational day 16, 3.03+/-0.25 at gestational day 19, 1.85+/-0.26 at gestational day 21) compared with control group(1.63+/-0.30, 4.16+/-0.45,2.55+/-0.26). Pulmonary AM (fmol/mg wet tissue) was decreased significantly at gestational day 19 and 21 in nitrofen group (4.51+/-0.78 at gestational day 19, 4.95+/-1.95 at gestational day 21): compared with control group (1.35+/-0.36,3.2+/-1.17), while there is no significantly deference at gestational day 16 (0.44+/-0.10 vs 0.46+/-0.13). Conclusion: Increased pulmonary expression of adrenomedullin in a rat model of CDH in the late gestation suggest that AM can be one of growth factors of the lung.