新生儿坏死性小肠结肠炎发病机制的新进展

刘娜; 李忠良; 张春磊; 李雪峰; 张成元; 张学博

doi:10.11852/zgetbjzz2020-2064

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中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (12) : 1309-1312. DOI: 10.11852/zgetbjzz2020-2064

综述

新生儿坏死性小肠结肠炎发病机制的新进展

刘娜, 李忠良, 张春磊, 李雪峰, 张成元, 张学博

作者信息 +

New progress in the pathogenesis of neonatal necrotizing enterocolitis

LIU Na, LI Zhong-liang, ZHANG Chun-lei, LI Xue-feng, ZHANG Cheng-yuan, ZHANG Xue-bo

Author information +

文章历史 +

摘要

新生儿坏死性小肠结肠炎(NEC)是新生儿发病率和死亡率较高的疾病之一。尽管新生儿的临床诊疗和护理等措施有所进步,但其未完全明确的发病机制仍是限制该疾病预后的主要原因。近几年,对该疾病发病机制的研究有了新的进展,包括血管内皮生长因子的调节,Toll 样受体的信号转导,通过代谢组学发现NEC潜在的生物标志物,探索NEC的遗传易感性,明确贫血和肠道菌群失调与NEC之间的关系。通过对NEC发病机理的深入了解有助于进一步提高对该疾病的诊疗。本文将对这些新的观点进行综述。

Abstract

Necrotizing enterocolitis (NEC) is one of the diseases with high morbidity and mortality in neonates. Although the clinical diagnosis, treatment and nursing of newborns have improved, the unclear pathogenesis is still the main reason that limits the prognosis of NEC. In recent years, new progress has been made in the research of the pathogenesis of NEC, including the modulation of vascular endothelial growth factor, the signal transduction of Toll-like receptors, the discovery of potential biomarkers of NEC through metabolomics, probing for genetic predispositions to NEC susceptibility, determining mechanistic relations between anemia, intestinal flora imbalance and NEC. In-depth understanding of the pathogenesis of NEC will help to further improve the diagnosis and treatment of this disease. In this article, these new insights will be reviewed.

导出引用

刘娜, 李忠良, 张春磊, 李雪峰, 张成元, 张学博. 新生儿坏死性小肠结肠炎发病机制的新进展[J]. 中国儿童保健杂志. 2021, 29(12): 1309-1312 https://doi.org/10.11852/zgetbjzz2020-2064

LIU Na, LI Zhong-liang, ZHANG Chun-lei, LI Xue-feng, ZHANG Cheng-yuan, ZHANG Xue-bo. New progress in the pathogenesis of neonatal necrotizing enterocolitis[J]. Chinese Journal of Child Health Care. 2021, 29(12): 1309-1312 https://doi.org/10.11852/zgetbjzz2020-2064

中图分类号： R722.1

参考文献

[1] Meister AL, Doheny KK, Travagli RA. Necrotizing enterocolitis: It's not all in the gut[J]. Exp Biol Med Maywood NJ,2020,245(2):85-95.
[2] Olm MR, Bhattacharya N, Crits-Christoph A, et al. Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella, and fimbriae-encoding bacteria[J]. Sci Adv,2019,5(12):eaax5727.
[3] Arthur CM, Nalbant D, Feldman HA, et al. Anemia induces gut inflammation and injury in an animal model of preterm infants[J]. Transfusion (Paris), 2019,59(4):1233-1245.
[4] Wang K, Tao G, Sylvester KG. Recent advances in prevention and therapies for clinical or experimental necrotizing enterocolitis[J]. Dig Dis Sci, 2019,64(11):3078-3085.
[5] Mohankumar K, Namachivayam K, Song T, et al. A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions[J]. Nat Commun,2019,10(1):3494.
[6] Bowker RM, Yan X, de Plaen IG. Intestinal microcirculation and necrotizing enterocolitis: The vascular endothelial growth factor system[J]. Semin Fetal Neonatal Med,2018,23(6):411-415.
[7] Bowker RM, Yan X, Managlia E, et al. Dimethyloxalylglycine preserves the intestinal microvasculature and protects against intestinal injury in a neonatal mouse NEC model: role of VEGF signaling[J]. Pediatr Res,2018,83(2):545-553.
[8] Sabnis A, Carrasco R, Liu SXL, et al. Intestinal vascular endothelial growth factor is decreased in necrotizing enterocolitis[J]. Neonatology, 2015,107(3):191-198.
[9] Niño DF, Zhou Q, Yamaguchi Y, et al. Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain[J]. Sci Transl Med,2018,10(471).doi:10.1126/scitranslmed.aan0237.
[10] Robinson JR, Kennedy C, van Arendonk KJ, et al. Neurodevelopmental considerations in surgical necrotizing enterocolitis[J]. Semin Pediatr Surg, 2018,27(1):52-56.
[11] Mihi B, Good M. Impact of Toll-like receptor 4 signaling in necrotizing enterocolitis: the state of the science[J]. Clin Perinatol,2019,46(1):145-157.
[12] Hackam DJ, Sodhi CP, Good M. New insights into necrotizing enterocolitis: from laboratory observation to personalized prevention and treatment[J]. J Pediatr Surg,2019,54(3):398-404.
[13] Shin SH, Kim EK, Yoo H, et al. Surgical necrotizing enterocolitis versus spontaneous intestinal perforation in white matter injury on brain magnetic resonance imaging[J]. Neonatology,2016,110(2):148-154.
[14] Cuna A, Sampath V. Genetic alterations in necrotizing enterocolitis[J]. Semin Perinatol,2017,41(1):61-69.
[15] Cuna A, George L, Sampath V. Genetic predisposition to necrotizing enterocolitis in premature infants: Current knowledge, challenges, and future directions[J]. Semin Fetal Neonatal Med,2018,23(6):387-393.
[16] Hackam DJ, Sodhi CP. Toll-like receptor-mediated intestinal inflammatory imbalance in the pathogenesis of necrotizing enterocolitis[J]. Cell Mol Gastroenterol Hepatol,2018,6(2):229-238.
[17] Wu W, Wang Y, Zou J, et al. Bifidobacterium adolescentis protects against necrotizing enterocolitis and upregulates TOLLIP and SIGIRR in premature neonatal rats[J]. BMC Pediatr,2017,17(1):1.
[18] Fawley J, Cuna A, Menden HL, et al. Single-immunoglobulin interleukin-1-related receptor regulates vulnerability to TLR4-mediated necrotizing enterocolitis in a mouse model[J]. Pediatr Res,2018,83(1-1):164-174.
[19] Lavoie S, Conway KL, Lassen KG, et al. The Crohn's disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response[J]. eLife,2019,8:e39982
[20] Sylvester KG, Kastenberg ZJ, Moss RL, et al. Acylcarnitine profiles reflect metabolic vulnerability for necrotizing enterocolitis in newborns born premature [J]. J Pediatr,2017,181:80-85.
[21] Sylvester KG, Ling XB, Liu GY, et al. A novel urine peptide biomarker-based algorithm for the prognosis of necrotizing enterocolitis in human infants[J]. Gut,2014,63(8):1284-1292.
[22] Jiang P, Trimigno A, Stanstrup J, et al. Antibiotic treatment preventing necrotising enterocolitis alters urinary and plasma metabolomes in preterm pigs[J]. J Proteome Res,2017,16(10):3547-3557.
[23] Call L, Stoll B, Oosterloo B, et al. Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC[J]. Microbiome,2018,6(1):111.
[24] 王朕,仰曙芬. 肠道菌群对新生儿坏死性小肠结肠炎影响的研究进展[J]. 中国儿童保健杂志,2020,28(11):1231-1233.
[25] Stewart CJ,Marrs EC,Nelson A,et al.Development of the preterm gut microbiome in twins at risk of necrotizing enterocolitis and sepsis[J].PLoS One,2013,8(8):e73465 .
[26] Underwood MA. Arguments for routine administration of probiotics for NEC prevention[J]. Curr Opin Pediatr,2019,31(2):188-194.
[27] Underwood MA, Arriola J, Gerber CW, et al. Bifidobacterium longum subsp. infantis in experimental necrotizing enterocolitis: alterations in inflammation, innate immune response, and the microbiota[J]. Pediatr Res,2014,76(4):326-333.
[28] Caplan MS, Underwood MA, Modi N, et al. Necrotizing enterocolitis: Using regulatory science and drug development to improve outcomes[J]. J Pediatr, 2019,212:208-215.
[29] Gephart SM, Gordon PV, Penn AH, et al. Changing the paradigm of defining, detecting, and diagnosing NEC: perspectives on Bell's stages and biomarkers for NEC[J]. Semin Pediatr Surg,2018,27(1):3-10.