血清缺氧诱导因子-1α、血管内皮生长因子及内皮素-1水平在新生儿缺氧性肺动脉高压中的变化及临床意义

Changes and clinical significance of serum hypoxia-inducible factor-1α, vascular endothelial growth factor and endothelin-1 levels in neonates with hypoxia-induced pulmonary hypertension

目的通过分析血清缺氧诱导因子-1α(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)中的变化,探讨此3种因子在新生儿HPH发病机制中的作用。方法选取2014年1月至2017年12月在我院新生儿重症监护室住院的50例HPH新生儿为HPH组,同期25例临床资料相似的非HPH住院新生儿为对照组,应用酶联免疫吸附法分别检测HPH被诊断时和肺动脉收缩压(PASP)降至35mmHg(1 mmHg=0.133kPa)以下时血清HIF-1α、VEGF及ET-1的水平,分析3种因子的水平变化并与同时间点对照组的水平进行比较。结果(1)HPH组新生儿的HIF-1α、VEGF及ET-1水平均较对照组水平明显增高,差异均有统计学意义(F值分别为151.97、43.31、129.56,P均<0.01),且HPH程度越重,其水平越高,差异均有统计学意义(P均<0.01)。(2)HPH组PASP降至35mmHg或以下后,血清HIF-1α、VEGF及ET-1水平也均明显下降,差异均有统计学意义(P均<0.01),除血清ET-1水平外,血清HIF-1α、VEGF水平与对照组的水平差异均无统计学意义(P均 >0.05)。结论缺氧引起HIF-1α、VEGF及ET-1水平升高,在新生儿HPH发生过程中起着重要作用。

Objective To analyze the changes of serum hypoxia-inducible factor-1α(HIF-1α), vascular endothelial growth factor(VEGF) and endothelin-1(ET-1) levels in neonates with hypoxia-induced pulmonary hypertension(HPH), and to explore the roles of three factors in the pathogenesis of HPH in neonates. Methods A total of 50 neonates with HPH in the neonatal intensive care unit as HPH group and another 25 non-HPH hospitalized neonates with similar clinical data in the same period as control group were enrolled from January 2014 to December 2017.The levels of serum HIF-1α, VEGF and ET-1 were determined by enzyme linked immunosorbent assay when neonates were diagnosed as HPH and their pulmonary artery systolic blood pressure(PASP) decreased to 35 mmHg below respectively.The changes of three factors levels were analyzed and compared with those of control group at the same time point. Results (1) The levels of serum HIF-1α, VEGF and ET-1 of HPH group were significantly higher than those of the control group (F value were 151.97, 43.31, and 129.56 respectively, all P<0.01). Furthermore, the more serious the grade of HPH, the higher the levels of three factors.The differences were statistically significant (all P<0.01). (2) After PASP of neonates in HPH group decreased to 35 mmHg or below, the levels of serum HIF-1α, VEGF and ET-1 also significantly decreased, and the differences were statistically significant (all P<0.01). However, there were no statistically significant differences compared with those of the control group for the levels of serum HIF-1α and VEGF(both P >0.05) in addition to serum ET-1 levels (F=14.98, P<0.05). Conclusion High levels of HIF-1α, VEGF and ET-1 caused by hypoxia may play an important role in neonatal HPH.