产前地塞米松可增强大鼠因硝呋烯腙诱导膈疝导致的肺发育不全肺组织中表面活性物质蛋白的合成。

Antenatal dexamethasone enhances surfactant protein synthesis in the hypoplastic lung of nitrofen-induced diaphragmatic hernia in rats.

作者信息

Guarino N, Oue T, Shima H, Puri P

机构信息

Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.

出版信息

J Pediatr Surg. 2000 Oct;35(10):1468-73. doi: 10.1053/jpsu.2000.16416.

DOI:10.1053/jpsu.2000.16416

PMID:11051153

Abstract

BACKGROUND/PURPOSE: Pulmonary hypoplasia is one of the main causes for the high mortality rate in patients with congenital diaphragmatic hernia (CDH). The expression of surfactant protein A in the hypoplastic CDH lung is reduced, and its concentration is decreased in the amniotic fluid of pregnancies complicated by CDH. In a CDH experimental model, prenatal glucocorticoid treatment has proved its efficacy in correcting the parameters of pulmonary biochemical and morphologic immaturity. The aim of this study was to investigate whether maternal administration of dexamethasone has any effect on the expression of surfactant protein A and surfactant protein B in nitrofen-induced experimental CDH rat model.

METHODS

CDH was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days). Dexamethasone (Dex, 0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n = 16); group II, nitrofen-induced CDH (n = 16); group III, nitrofen-induced CDH with antenatal Dex treatment (n = 16). Indirect immunohistochemistry was performed using alkaline-phosphatase-coagulated streptavidin using anti-SP-A and anti-SP-B polyclonal antibodies. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate relative amount of SP-A and SP-B mRNA expression.

RESULTS

In the CDH lung (group II) we observed a markedly reduced number of type II pneumocytes positive for SP-A, and SP-B was increased to a level close to that of the control group. The relative amount of SP-A and SP-B was reduced significantly in group II compared with controls (P < .05) and significantly increased in group III compared with group II animals (P < .01).

CONCLUSION

These results suggest that antenatal glucocorticoid treatment increases the production of surfactant proteins in the CDH hypoplastic lung.

摘要

背景/目的：肺发育不全是先天性膈疝（CDH）患者高死亡率的主要原因之一。在发育不全的CDH肺中，表面活性蛋白A的表达降低，且在合并CDH的妊娠羊水中其浓度下降。在一个CDH实验模型中，产前糖皮质激素治疗已证明其在纠正肺生化和形态学不成熟参数方面的疗效。本研究的目的是调查母体给予地塞米松对硝呋烯腙诱导的实验性CDH大鼠模型中表面活性蛋白A和表面活性蛋白B的表达是否有任何影响。

方法

在妊娠第9.5天（足月为22天）给孕鼠腹腔注射100 mg硝呋烯腙诱导CDH。在妊娠第18.5天和第19.5天通过腹腔注射给予地塞米松（Dex，0.25 mg/kg）。在妊娠第21天进行剖宫产。将胎儿分为3组：I组，对照组（n = 16）；II组，硝呋烯腙诱导的CDH组（n = 16）；III组，产前给予Dex治疗的硝呋烯腙诱导的CDH组（n = 16）。使用抗SP-A和抗SP-B多克隆抗体，采用碱性磷酸酶-凝固链霉亲和素进行间接免疫组织化学。进行逆转录聚合酶链反应（RT-PCR）以评估SP-A和SP-B mRNA表达的相对量。