探讨血清缺氧诱导因子(HIF)-1α、血管内皮生长因子(VEGF)、内皮素-1(ET-1)水平，在新生儿缺氧性肺动脉高压(HPH)患儿中的变化及其与肺动脉收缩压(PASP)的关系。

选取2014年1月12日至2017年12月19日，于南方医科大学附属花都医院新生儿科住院治疗的50例HPH新生儿为研究对象，纳入HPH组。根据HPH组新生儿PASP的不同，将其进一步分为中/重度HPH亚组(n＝22，PASP>50 mmHg)与轻度HPH亚组(n＝28，PASP为35～50 mmHg)，1 mmHg＝0.133 kPa。选取同期于本院新生儿科住院治疗的25例出生胎龄、日龄、性别、分娩方式、血清标本留取时间与HPH组匹配的非HPH新生儿(动态PASP<35 mmHg)，纳入对照组。分别采用酶联免疫吸附测定(ELISA)法与超声心动图检测HPH组与对照组受试儿血清HIF-1α、VEGF、ET-1水平，以及PASP。HPH组与对照组血清HIF-1α、VEGF、ET-1水平比较，采用成组t检验；对中/重度HPH亚组、轻度HPH亚组与对照组上述指标比较，采用单因素方差分析，进一步两两比较，采用LSD法。血清HIF-1α、VEGF、ET-1水平与PASP的相关性，以及这3种因子之间的相关性，采用Pearson相关性分析。本研究通过南方医科大学附属花都医院医学伦理委员会审查(审批文号：14-HDWS-001)。HPH组与对照组患儿胎龄、日龄及性别、分娩方式、基础疾病构成比比较，差异均无统计学意义(P>0.05)。

①HPH组患儿血清HIF-1α、VEGF及ET-1水平分别为(686.3±235.9)、(154.7±63.0)、(164.3±115.3) pg/mL，对照组分别为(260.9±132.0)、(96.2±30.3)、(41.9±3.7)pg/mL，HPH组患儿血清HIF-1α、VEGF及ET-1水平，均较对照组明显增高，2组比较，差异均有统计学意义(t＝8.336、4.388、5.288，P<0.001)。中/重度HPH亚组、轻度HPH亚组、对照组患儿血清HIF-1α、VEGF、ET-1水平分别整体比较，差异均有统计学意义(F＝156.362、36.956、67.464，P<0.001)，进一步两两比较的结果显示，差异亦均有统计学意义(P<0.001)，并且HPH病情越严重，这3种因子的血清水平越高。②所有患儿的血清HIF-1α、VEGF及ET-1水平，与其PASP均呈正相关关系(r＝0.941、0.780、0.864，P<0.001)。③所有患儿的血清VEGF、ET-1水平与其血清HIF-1α水平均呈正相关关系(r＝0.806、0.850，P<0.001)。

缺氧可诱导新生儿HIF-1α表达增多，并上调VEGF及ET-1表达。HIF-1α可能在新生儿HPH发生过程中起着重要作用。

To explore the changes of serum hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in neonatal hypoxic pulmonary hypertension (HPH) and the relationship with pulmonary systolic blood pressure (PASP).

From January 12, 2014 to December 19, 2017, a total of 50 HPH neonates hospitalized in the Department of Neonatology, Huadu Hospital Affiliated to Southern Medical University were selected as research subjects and included into HPH group. According to PASP of HPH neonates, 50 HPH neonates were further divided into moderate/severe HPH subgroup (n=22, PASP was > 50 mmHg) and mild HPH subgroup (n=28, PASP was 35-50 mmHg), 1 mmHg=0.133 kPa. Meanwhile, another 25 non-HPH neonates (dynamic PASP was < 35 mmHg) hospitalized in the Department of Neonatology during the same period in the same hospital were selected as control group. Their gestational age at birth, day age, gender, mode of delivery and serum sample retention time were matched to those in HPH group . The levels of serum HIF-1α, VEGF and ET-1 were detected by enzyme linked immunosorbent assay (ELISA) method, and their PASP were estimated by echocardiography. Independent-samples t test was used for the comparison of serum HIF-1α, VEGF and ET-1 levels between HPH group and control group, while one-way ANOVA was used for the comparison among moderate/severe HPH subgroup, mild HPH subgroup and control group, and further pairwise comparison were analyzed by LSD method. Pearson correlation analysis was applied for the correlation between serum HIF-1α, VEGF, ET-1 levels and PASP, as well as between these three factors. This study was approved by the Ethics Committee of Human Beings in Huadu Hospital Affiliated to Southern Medical University (Approval Number: 14-HDWS-001). There were no statistically significant differences between HPH group and control group in gestational age, day age, and constituent ratios of gender, delivery mode and basic diseases (P>0.05).

①The levels of serum HIF-1α, VEGF and ET-1 were (686.3 ± 235.9) g/mL, (154.7 ± 63.0) g/mL and (164.3 ± 115.3) pg/mL, respectively in HPH group. Those in control group were (260.9 ±132.0) g/mL, (96.2 ± 30.3) g/mL, (41.9 ± 3.7) pg/mL, respectively. The levels of serum HIF-1α, VEGF and ET-1 in HPH group were significantly higher than those in control group, and all the differences were statistically significant (t=8.336, 4.388, 5.288; P<0.001). There were statistically significant differences among moderate/severe HPH subgroup, mild HPH subgroup and control group in levels of serum HIF-1α, VEGF and ET-1 (F=156.362, 36.956, 67.464; P<0.001). For further pairwise comparison among those three groups, there were statistically significant differences between each groups in the aspects of levels of serum HIF-1α, VEGF and ET-1 (P<0.001). Furthermore, the higher the severity of HPH, the higher the serum levels of these three factors. ②Among all the subjects, the levels of serum HIF-1α, VEGF and ET-1 were positively correlated with PASP (r=0.941, 0.780, 0.864; P<0.001). ③The levels of serum VEGF and ET-1 were positively correlated with the level of serum HIF-1α among all the subjects (r=0.806, 0.850; P<0.001).

Hypoxia environment can induce increased expression of HIF-1α and upregulate the expression of VEGF and ET-1 through HIF-1α, which may play an important role in the development of neonatal HPH.