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

背景/目的：尽管近年来肺发育不良的治疗取得了很大进展，但先天性横隔疝(CDII)合并肺发育不良的预后仍然很差，但胎儿和新生儿时期的肺发育被认为是更重要的因素。肾上腺髓质素(adrenomedullin，AM)是一种新的血管扩张多肽，也被发现在胎儿肺的分化和成熟机制中发挥作用。在这项研究中，我们检测了肾上腺髓质素在CDH大鼠模型中的表达。方法：定时妊娠SD大鼠(足月22天)，于孕9.5天给予400 mg/kg的硝苯醚，于孕16、19、21天取胎肺，建立先天性腹股沟疝气模型。在对照组动物中，给予相同剂量的橄榄油，但不含硝苯醚。测定硝苯芬组和对照组的肺/体重比和肺组织AM。结果：与对照组(1.63+/-0.30，4.16+/-0.45，2.55+/-0.26)相比，硝苯芬组的肺/体重比(%)显著降低(孕16天1.24±0.13，孕19天3.03+/-0.25，孕21天1.85+/-0.26)。与对照组(1.35+/-0.36，3.2+/-1.17)相比，硝苯芬组在孕19天和21天肺AM(fmoL/mg湿组织)显著降低(分别为4.51±0.78和4.95±1.95)，而在孕16天差异无统计学意义(0.44+/-0.10比0.46+/-0.13)。结论：妊娠晚期CDH大鼠肺组织肾上腺髓质素表达增加，提示AM可能是肺的生长因子之一。

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.