益生菌对纯配方奶喂养极低出生体重儿细胞因子的影响

Effects of probiotics on blood cytokines in very low birth weight infants with formula feeding

目的了解口服益生菌对纯配方奶喂养极低出生体重儿血细胞因子的影响。方法选取2014年7月1日至2015年12月31日生后24h内入住深圳市宝安区妇幼保健院新生儿重症监护病房（Neonatal intensive care unit，NICU），胎龄〈34周、出生体重〈1500g的极低出生体重儿（Very low birth weight infant，VLBWI）为研究对象，随机分为益生菌组（n=20）和对照组（n=20），采用多通道流式细胞术分别于生后24h内、14d、28d、纠正胎龄36周4个时间点检测血清IL-2、IL-4、IL-6、IL-8、IL-10、GM-CSF、IFN-γ、TNF-α、MIG等9种细胞因子水平，比较两组在临床并发症和细胞因子表达方面的差异。结果存临床合并症方面，益生菌组患儿合并坏死性小肠结肠炎（NEC）、晚发性败血症、静脉营养相关性胆汁淤积症的比例均低于对照组，但差异无统计学意义（P〉0．05）；在血细胞因子表达方面，NEC或死产组VLBWI血清IL-6水平明显高于非NEC或死亡组（94．91pg／ml比5．71pg／ml，P〈0．05）；在VLBWI合并败血症患儿中，口服益生菌生后14d时札清IL-8、IFN-γ水平明显低于对照组（7．83pg／nd比40．58pg／ml、7．68pg/ml比9．45pg／ml，P〈0．05）；在住院期间相对稳定VLBWI中，口服益生菌患儿在纠正胎龄36周时，血清IL-2、IL-4、GM-CSF水平明显高于对照组（7．33pg／ml比6．0pg／ml、0．37pg／ml比0.3lpg／ml、12．53pg／ml比8．85pg／ml，P〈0．05）。结论益生菌可下渊促炎因子和上凋抑炎因子水平，保持抗炎和抑炎因子的动态失衡，在预防极低出生体重儿发生坏死性小肠结肠炎和死亡并发症方面有一定的保护作用。

Objective To explore the effects of oral probiotics on blood cytokines among very low birth weight infants （VLBWI） with formula feeding. Methods Preterm infants born at 〈34 weeks gestational age （GA） and birth weight （BW） 〈1500 g admitted to NICU of our hospital from Jul.1, 2014 to Dec. 31, 2015 were enrolled and randomly divided into probiotics group and control group. The levels of blood cytokine, including IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ, TNF-α, MIG were analyzed with multiplex flow cytometry within 24 h after birth, on the postnatal 14th and 28th day, and in the 36th week corrected GA. The clinical complications and changes of blood cytokines were compared between the two groups. Results The incidences of necrotizing enterocolitis （NEC）, late-onset sepsis （LOS）, parenteral nutrition associated cholestasis （PNAC） in the probiotics group were lower than those in the control group, but without statistically significant differences （P〉0.05）. The level of blood IL-6 was much higher in the NEC or death group than the others （94.91 pg/ml vs.5.71 pg/ml, P〈0.05）. In the septic infants, the levels of blood IL-8, IFN-γ in the probiotics group on the postnatal 14th day were significantly lower than those in the control group （7.83 pg/ml vs.40.58 pg/ml, 7.68 pg/ml vs.9.45 pg/ml; P〈0.05）. In the stable infants, the levels of blood IL-2, IL-4, GM-CSF in the probiotics group in the 36th week corrected GA were significantly higher than those in the control group （7.33 pg/ml vs.6.0 pg/ml, 0.37 pg/ml vs.0.31 pg/ml, 12.53 pg/ml vs.8.85 pg/ml; P〈0.05）. Conclusion Probiotics decreased the expression of pro-inflammatory factors and increased the expression of anti-inflammatory factors, which may play a protective role in the prevention of NEC or death in VLBWI with formula feeding through regulating the balance between pro- and anti-inflammatory factors.