外周血内皮祖细胞与极低出生体重早产儿并发症发生相关性

Association between peripheral endothelial progenitor cells and the development of premature birth complications in infants with very low birth weight

目的分析内皮祖细胞(EPCs)与极低出生体重早产儿发生支气管肺发育不良(BPD)、早产儿视网膜病(ROP)和脑室内出血(IVH)并发症的相关性。方法选取于复旦大学附属儿科医院NICU住院的胎龄<32周、出生体重<1 500g的早产儿,分别于出生时、生后7、14、21和28 d及纠正胎龄36周时收集外周血,流式细胞仪检测EPCs水平,酶联免疫法检测血管内皮生长因子(VEGF)、基质细胞衍生因子等水平。结果 68例极低出生体重早产儿纳入分析,其中对照组30例,BPD组20例,ROP组10例,IVH组8例。BPD组与对照组出生时EPCs水平差异无统计学意义,生后7 d时点EPCs水平较对照组明显降低,CD34+KDR+:(0.019±0.009)%vs(0.026±0.012)%,P<0.05;KDR+CD133+:(0.004±0.002)%vs(0.008±0.004)%,P<0.01;CD34+KDR+CD133+:(0.005±0.002)%vs(0.008±0.004)%,P<0.05。从出生时至生后21 d,BPD组血浆VEGF水平均明显低于对照组。ROP组出生时至生后28 d的EPCs水平与对照组差异无统计学意义,纠正胎龄36周时KDR+CD133+和CD34+KDR+CD133+EPCs与对照组相比略有升高趋势。与对照组相比,IVH组生后不同时点的EPCs水平差异均无统计学意义。结论生后早期的EPCs和VEGF水平降低可能参与了早产儿BPD的发生,但其具体机制仍需进一步研究。

Objective To investigate the association of endothelial progenitor cells （EPCs） with the development of bronchopulmonary dysplasia （ BPD）, retinopathy of prematurity （ROP） and other complications in infants with very low birth weight. Methods Infants with gestational age less than 32 weeks and birth weight below 1 500 g were prospectively selected who were hospitalized at neonatal intensive care unit. EPCs level was determined by flow cytometry at different time points （ at birth, 7, 14, 21,28 days of age and 36 weeks＇postmenstrual age）. Plasma vascular endothelial growth factor （VEGF） , stromal cell-derived factor-1 （SDF-1） and granulocyte-macrophage colony-stimulating factor （GM-CSF） concentrations were determined by immunochemical assays. Clinical and outcome data were collected. Results Sixty-eight infants were analyzed in this study, including 20 who developed BPD, 10 developed ROP, 8 had intraventricular hemorrhage （IVH） comprising case groups, and rest of 30 patients as control group. No difference was observed in the number of EPCs at birth between BPD infants and control infants. Compared with the control group, EPCs level decreased at day 7, CD34 ＋ KDR ＋ ： （0.019 ＋ 0. 009） % vs （0. 026 ＋ 0.012） %, P〈O.05; KDR＋CD133＋ ： （0.004＋0.002）% vs （0.008 ＋0.004）%, P〈O. O1; CD34＋KDR＋CD133＋ ： （0.005 ＋0.002）% vs （0. 008 ＋ O. 004）%, P 〈 O. 05 and day 21 in infants who later developed BPD. BPD infants had persistent lower VEGF concentration compared with the control infants at all time points from birth to day 21. No between - group difference in VEGF was found at day 28 or 36 weeks＇postmenstrual age. There was no difference in the concentrations of SDF-1 and GM-CSF at different time points between two groups. No different was observed in EPCs count between infants with ROP and the control infants at any time points from birth to day 28. However, a trend of increasing KDR＋ CD133＋ , （0. 010 ＋0. 003）% vs （0. 007 ＋0. 003）%, P=0.053, and CD34＋KDR＋CD133＋ EPCs ,（0.009 ＋0.005）% vs （0.006 ＋ 0.003）%, P=O. 06, was noted in the infants with ROP at the 36 weeks postmenstrual age. EPCs count did not differ between infants with IVH and the controls infants at different time point. Conclusion Reduced EPCs and VEGF level at early life may be associated with development of BPD in preterm infants. However, the exact mechanism underlying the EPCs and BPD needs further investigation.