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Effect of Bifidobacterium on the expression of β-defensin-2 in intestinal tissue of neonatal rats with necrotizing enterocolitis
LU Wei-Cheng, ZHENG Xu, LIU Jin-Fu, WU Wen-Chuan, CHEN Xing-Yue, WEI Hai-Bo, LI Chun-Lei, LIN Ming-Jing
Chinese Journal of Contemporary Pediatrics ›› 2018, Vol. 20 ›› Issue (3) : 224-229.
PDF(1666 KB)
PDF(1666 KB)
Effect of Bifidobacterium on the expression of β-defensin-2 in intestinal tissue of neonatal rats with necrotizing enterocolitis
Objective To study the effect of Bifidobacterium on the expression of β-defensin-2 (BD-2) in intestinal tissue of neonatal rats with necrotizing enterocolitis (NEC). Methods A total of 40 rats were randomly divided into four groups:normal control, Bifidobacterium control, NEC model, and Bifidobacterium treatment, with 10 rats in each group. A rat model of NEC was induced by hypoxia, cold stimulation, and artificial feeding. The rats in the Bifidobacterium control and Bifidobacterium treatment groups were given Bifidobacterium via the gastric tube after cold stimulation once a day for three consecutive days. The morphological changes of the terminal ileum were observed under a light microscope and the intestinal injury score was determined. Immunohistochemistry and qRT-PCR were used to measure the protein and mRNA expression of BD-2 in the ileal mucosal tissue. Results The NEC model group had a significantly higher intestinal injury score than the normal control, Bifidobacterium control, and Bifidobacterium treatment groups (P < 0.05). The Bifidobacterium treatment group had a significantly higher intestinal injury score than the normal control and Bifidobacterium control groups (P < 0.05). The mRNA and protein expression of BD-2 in the normal control group was significantly lower than in the Bifidobacterium control, NEC model, and Bifidobacterium treatment groups (P < 0.05). The Bifidobacterium control group had significantly higher mRNA and protein expression of BD-2 than the NEC model and Bifidobacterium treatment groups (P < 0.05). The Bifidobacterium treatment group had significantly higher mRNA and protein expression of BD-2 than the NEC model group (P < 0.05). Conclusions Bifidobacterium can induce the expression of BD-2 in intestinal tissue of rats and reduce inflammatory response by increasing the expression of BD-2. This provides a protective effect on neonatal rats with NEC.
β-defensin-2 / Necrotizing enterocolitis / Bifidobacterium / Neonatal rats
[1] Neu J, Walker WA. Necrotizing enterocolitis[J]. N Engl J Med, 2011, 364(3):255-264.
[2] Halpern MD, Denning PW. The role of intestinal epithelial barrier function in the development of NEC[J]. Tissue Barriers, 2015, 3(1-2):e1000707.
[3] Kim MJ, Lee WY, Choe YH. Expression of TIM-3, human β-defensin-2, and FOXP3 and correlation with disease activity in pediatric Crohn's disease with infliximab therapy[J]. Gut Liver, 2015, 9(3):370-380.
[4] Underwood MA. Probiotics and innate and adaptive immune responses in premature infants[J]. For Immunopathol Dis Therap, 2016, 7(1-2):1-15.
[5] Costeloe K, Hardy P, Juszczak E, et al. Bifidobacterium breve BBG-001 in very preterm infants:a randomized controlled phase 3 trial[J]. Lancet, 2016, 387(10019):649-660.
[6] AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants[J]. Evid Based Child Health, 2014, 9(3):584-671.
[7] 盛庆丰, 吕志葆, 蔡威, 等. 重组人β-防御素3干预新生大鼠坏死性小肠结肠炎模型的研究[J]. 中华小儿外科杂志, 2015, 36(2):109-112.
[8] Nadler EP, Dickinson E, Knisely A, et al. Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis[J]. J Surg Res, 2000, 92(1):71-77.
[9] Birner P, Schindl M, Obermair A, et al. Overexpression of hypoxia-inducible factor 1 alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer[J]. Cancer Res, 2000, 60(17):4693-4696.
[10] 何彦册, 贺湘英, 黄永坤, 等. 酪酸梭菌对坏死性小肠结肠炎新生鼠肠损伤的保护作用[J]. 临床儿科杂志, 2016, 34(7):547-552.
[11] Denning TL, Bhatia AM, Kane AF, et al. Pathogenesis of NEC:Role of the innate and adaptive immune response[J]. Semin Perinatol, 2017, 41(1):15-28.
[12] Battersby AJ, Khara J, Wright VJ, et al. Antimicrobial proteins and peptides in early life:ontogeny and translational opportunities[J]. Front Immunol, 2016, 7:309.
[13] Weitkamp JH, Koyama T, Rock MT, et al. Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios[J]. Gut, 2013, 62(1):73-82.
[14] Trend S, Strunk T, Hibbert J, et al. Antimicrobial protein and Peptide concentrations and activity in human breast milk consumed by preterm infants at risk of late-onset neonatal sepsis[J]. PLoS One, 2015, 10(2):e0117038.
[15] Olbrich P, Pavón A, Rosso ML, et al. Association of human beta-defensin-2 serum levels and sepsis in preterm neonates[J]. Pediatr Crit Care Med, 2013, 14(8):796-800.
[16] Richter M, Topf HG, Gröschl M, et al. Influence of gestational age, cesarean section, and type of feeding on fecal human beta-defensin 2 and tumor necrosis factor-alpha[J]. J Pediatr Gastroenterol Nutr, 2010, 51(1):103-105.
[17] Campeotto F, Baldassarre M, Laforgia N, et al. Fecal expression of human β-defensin-2 following birth[J]. Neonatology, 2010, 98(4):365-369.
[18] Jenke AC, Zilbauer M, Postberg J, et al. Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis[J]. Pediatr Res, 2012, 72(5):513-520.
[19] Patel RM, Denning PW. Intestinal microbiota and its relationship with necrotizing enterocolitis[J]. Pediatr Res, 2015, 78(3):232-238.
[20] 郭城, 张琳. 益生菌在新生儿坏死性小肠结肠炎中的应用[J]. 中国实用儿科杂志, 2017, 32(2):120-125.
[21] Jenke AC, Postberg J, Mariel B, et al. S100A12 and hBD2 correlate with the composition of the fecal microflora in ELBW infants and expansion of E. coli is associated with NEC[J]. Biomed Res Int, 2013, 2013:150372.
[22] 李阳, 余加林, 艾青, 等. 早产儿坏死性小肠结肠炎肠道菌群多样性及其动态研究[J]. 中国循证儿科杂志, 2014, 9(2):117-121.
[23] Habil N, Abate W, Beal J, et al. Heat-killed probiotic bacteria differentially regulate colonic epithelial cell production of human β-defensin-2:dependence on inflammatory cytokines[J]. Beneficial Microbes, 2014, 5(4):483-495.
[24] Yoon YM, Lee JY, Yoo D, et al. Bacteroides fragilis enterotoxin induces human beta-defensin-2 expression in intestinal epithelial cells via a mitogen-activated protein kinase/I kappaB kinase/NF-kappaB-dependent pathway[J]. Infect Immun, 2010, 78(5):2024-2033.
[25] Lewis SB, Prior A, Ellis SJ, et al. Flagellin induces β-defensin 2 in human colonic Ex vivo infection with enterohemorrhagic Escherichia coli[J]. Front Cell Infect Microbiol, 2016, 6:68.
[26] Omagari D, Takenouchi-Ohkubo N, Endo S, et al. Nuclear factor kappa B plays a pivotal role in polyinosinic-polycytidylic acid-induced expression of human β-defensin 2 in intestinal epithelial cells[J]. Clin Exp Immunol, 2011, 165(1):85-93.
