HIF-1α、ET-1和iNOS在新生儿缺氧性肺动脉高压发病中的作用

Role of hypoxia-inducible factor-1α endothelin-1 and inducible nitric oxide synthase in the pathogenesis of hypoxia-induced pulmonary hypertension of the newborn

摘要:

目的：探讨缺氧诱导因子-1α（HIF-1α）、内皮素-1（ET-1）、诱导型一氧化氮合酶（iNOS）在新生儿缺氧性肺动脉高压（HPH）发病机制中的意义。方法：选取2006年6月至2009年11月在我院住院的75例足月HPH新生儿（轻度29例，中度25例，重度21例)）及足月非HPH新生儿22例（对照组），于生后1、3、7 d采用ELASA测定血清HIF-1α、iNOS和ET-1水平。结果：生后第1天，轻、中、重度HPH组血清HIF-1α和ET-1较对照组升高（P＜0.01），而且随着HPH程度的加重，HIF-1α和ET-1逐渐增高（P＜0.05）；中、重度组血清iNOS较对照组升高（P＜0.01）。生后第3天时，中度组血清ET-1，重度组血清HIF-1α、ET-1和iNOS较对照组升高（P＜0.05）。生后第7天时，重度组血清ET-1仍高于对照组（P＜0.05）。结论：HPH患儿血清HIF-1α、ET-1及iNOS水平升高，导致ET-1与NO平衡失调，这可能在HPH发生中起了重要的作用。

Abstract:

OBJECTIVE: To investigate the roles of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) of the newborn. METHODS: Seventy-five term hospitalized neonates with HPH (mild 29 cases, moderate 25 cases, severe 21 cases) and 22 term hospitalized neonates without HPH (control group) were enrolled between June 2006 and November 2009. Serum levels of HIF-1α, iNOS and ET-1 were measured using ELASA 1, 3 and 7 days after birth. RESULTS: Serum concentrations of HIF-1α and ET-1 in the mild, moderate and severe HPH groups were significantly higher than those in the control group (P<0.01) 1 day after birth, and were related to the severity of HPH. The serum iNOS concentrations in the moderate and severe HPH groups were also significantly higher than those in the control group (P<0.01). By 3 days after birth, serum ET-1 concentration in the moderate HPH group and serum concentrations of HIF-1α, ET-1and iNOS in the severe HPH group reminded significantly higher than those in the control group (P<0.05). At 7 days after birth, serum ET-1 concentration in the severe HPH group still remained higher than that in the control group (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, ET-1 and iNOS increase in neonates with HPH, resulting in an imbalance of ET-1 and NO. This may be of importance in the pathogenesis of neonatal HPH.