Oxygen promoted bFGF-induced Intimal Thickening

出生后动脉导管未闭(DA)是早产儿发病率和死亡率的主要原因。DA在出生后立即收缩，对急性氧合和胎盘前列腺素的停止做出反应。然而，为了完全闭合，DA区还必须进行内膜增厚。目前尚不清楚DA的内膜增厚是如何在出生后进行的。在这里，我们展示了氧合诱导体内DA中碱性成纤维细胞生长因子(BFGF)的产生。碱性成纤维细胞生长因子诱导内膜增厚，导致DA的解剖闭合。碱性成纤维细胞生长因子联合小剂量环氧合酶抑制剂可使早产儿DA闭合。因此，除引起收缩外，氧合作用在前列腺素去除后完成DA关闭过程中也起着重要作用。因此，目前的血管收缩疗法可能与出生后内膜增厚的诱导剂，如碱性成纤维细胞生长因子联合使用，以实现DA的永久性闭合，特别是在早产儿。

Postnatal patent ductus arteriosus (DA) is a major cause of morbidity and mortality in premature infants. The DA contracts immediately after birth in response to acute oxygenation and the withdrawal of placental prostaglandin. For complete closure, however, the DA region must also undergo intimal thickenings. It remains unknown how intimal thickening of the DA proceeds after birth. Here, we show that oxygenation induces basic fibroblast growth factor (bFGF) production in the DA in vivo. bFGF induced intimal thickening, leading to anatomical closure of the DA. bFGF with a low dose of cyclooxygenase inhibitor achieved the closure of preterm DA. Accordingly, oxygenation, in addition to inducing contraction, plays an important role in completing DA closure after prostaglandin removal. The current vasoconstrictor therapy may thus be combined with an inducer of postnatal intimal thickening, such as bFGF, to achieve permanent DA closure, especially in premature infants.