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.
Key words
Hypoxia-induced pulmonary hypertension /
Hypoxia-inducible factor-1α /
Endothelin-1 /
Inducible nitric oxide synthase /
Neonate
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References
［1］李玖军, 韩晓蕾, 魏克伦. 新生儿呼吸窘迫综合症肺动脉压力动态变化及其与血清内皮素1和一氧化氮关系的研究［J］. 中华儿科杂志, 2001, 39(11):678681.
［2］He ZH, Dai AG, Zhang XF, Tan XW. Expressions of hypoxia inducible factor-1 alpha and inducible nitric oxide synthase gene in the development of hypoxic pulmonary hypertension in rats［J］. Clin Rehab Tissue Eng Res, 2007,11(36): 7290-7294.
［3］McQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects［J］. Circulation, 2001,104(23): 2797-2802.
［4］Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, et al. Clinical classification of pulmonary hypertension［J］. J Am Coll Cardiol, 2004, 43(12 Suppl S): 5S-12S.
［5］Stephen B, Dalal P, Berger M, Schweitaer P, Hecht S. Noninvasive estimation of pulmonary artery diastolic pressure in patients with tricuspid regurgitation by Doppler echocardiography［J］. Chest, 1999, 116(1):73-77.
［6］Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ. Echocardiographic determination of mean pulmonary artery pressure［J］. Am J Cardiol, 2003, 92(11): 1373-1376.
［7］Ruas JL, Lendahl U, Poellinger L.Modulation of vascular gene expression by hypoxia［J］. Curr Opin Lipidol, 2007,18(5): 508-514.
［8］Rajatapiti P, van der Horst IW, de Rooij JD, Tran MG, Maxwell PH, Tibboel D, et al. Expression of hypoxia-inducible factors in normal human lung development［J］. Pediatr Dev Pathol, 2008,11(3): 193-199.
［9］Schindler MB, Hislop AA, Haworth SG. Porcine pulmonary artery and bronchial responses to endothelin-1 and norepinephrine on recovery from hypoxic pulmonary hypertension［J］. Pediatr Res, 2006, 60(1): 71-76.
［10］Hu R, Dai A, Tan S. Hypoxia-inducible factor 1 alpha upregulates the expression of inducible nitric oxide synthase gene in pulmonary arteries of hypoxic rat［J］. Chin Med J(Engl), 2002, 115(12): 1833-1837.
［11］敖启林, 郝春荣, 熊密,王迪浔. 低氧诱导因子-1α和内皮素-1基因在大鼠低氧性肺动脉高压中的表达［J］. 中华病理学杂志, 2002, 31(2):140-142.
［12］Jung F, Palmer LA, Zhou N, Johns RA. Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes［J］. Circ Res, 2000, 86(3): 319-325.
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