[Effect of hemin on the lung development and pulmonary arterial structural remodeling in congenital diaphragmatic hernia: experiment with rats].

OBJECTIVE

To assay the effects of prenatal hemin therapy on pulmonary hypoplasia (PH) and pulmonary arterial structural remodeling in congenital diaphragmatic hernia (CDH).

METHODS

Six pregnant female SD rats were randomly divided into 3 equal groups: control group, undergoing gastric perfusion of olive oil once on day 9.5 and intraperitoneal injection of normal saline on days 11-14; CDH group, undergoing gastric perfusion of nitrofen 125 mg once on day 9.5 and intraperitoneal injection of normal saline on days 11-14; and hemin group, undergoing gastric perfusion of nitrofen 125 mg once on day 9.5 and intraperitoneal injection of hemin 15 mg x kg(-1) x d(-1) on days 11-14. On the gestational day 21 caesarean section was performed to take out the fetuses to undergo histological examination and image analysis.

RESULTS

CDH were detected in 28 of the 44 (63.6%) fetuses from the 2 groups receiving nitrofen. The lungs of all CDH group fetuses were hypoplastic, and the fetuses of the hemin group showed improved lung development. The right lung/body weight ratio and pulmonary alveolar area ratio (PAA%) of the hemin group were (16.6 +/- 1.0) mg/g and (45 +/- 6)% respectively, both significantly higher than those of the CDH group [(14.6 +/- 1.7) mg/g and (28 +/- 6)% respectively, P = 0.03 and P < 0.01]. The alveolar septum area ratio (ASA%) of the hemin group was (44 +/- 6)%, significantly lower than that of the CDH group [(64 +/- 8)%, P < 0. 01]. The media thickness percentages (MT%) of pre-acinar artery (PAPA) and intra-acinar artery (IAPA) of the fetuses of the hemin group were (21.2 +/- 2.2)% and (18.2 +/- 2.1)% respectively, both significantly lower than those of the CDH group [(24.3 +/- 4.0)% and (21.9 +/- 3.9)% respectively, both P < 0.05], which were significantly higher than those of the control group [(20.0 +/- 2.4)% and (17.2 +/- 2.3)% respectively, both P < 0.01]. The component ratio of nonmuscularized artery (NMA) in the IAPA level of the hemin group was (78.2 +/- 3.0)%, significantly higher than that of the CDH group [(72.8 +/- 3.2)%, P = 0.001].

CONCLUSION

PH and pulmonary arterial structural remodeling are present in CDH. Although prenatal administration of hemin cannot prevent the genesis of CDH in rats, it may improve the pulmonary development, inhibit medial hypertrophy, and reduce the percentage of muscularized IAPA.