目的 研究双歧杆菌在预防新生鼠坏死性小肠结肠炎中应用剂量的问题,为临床合理用药提供理论依据。方法 选取新生SD大鼠40只,随机分为5组:A,正常对照组;B,NEC模型组;C,NEC模型组,每日给予0.4 mg/g的酪酸梭菌二联活菌散(主要有效成分为双歧杆菌)灌胃;D,NEC模型组,每日给予4 mg/g酪酸梭菌二联活菌散灌胃;E,NEC模型组,每日给予20 mg/g酪酸梭菌二联活菌散灌胃。每日记录体重;3 d后禁食1 d,处死所有新生鼠,取血检测TNF-α并对比;HE染色法观察肠道组织。结果 体重变化均值为A>D>E>C>B,除B与C间,D与E间差异无统计学意义,其余组两两对比差异均有统计学意义。HE染色评分均值为B>D>C>E>A,仅A与其他各组间差异有统计学意义。TNF-α均值为B>C>D>E>A,除B与C间,D与E间差异无统计学意义,其余组间均有统计学意义。综合分析,D、E的炎症程度低于B、C。结论 酪酸梭菌二联活菌散在新生鼠NEC中应用的最佳预防剂量可能为4~20 mg/g,相当于双歧杆菌4.0×103~20×103CFU。
Abstract
Objective To study the dose of bifidobacteria in preventing neonatal necrotizing enterocolitis (NEC) in newborn rats,and to provide theoretical for clinical rational drug use. Methods A total of 40 SD rats were divided into 5 groups randomly:A,the normal group;B,NEC model group,give them lavage with normal saline daily while making model;C,NEC model group,establish the model and give 0.4 mg/g of duplex butyric acid bacteria living bacterium(Its main effective components is bifidobacterium)to fill the stomach daily;D,NEC model group,established the model and give 4 mg/g of duplex butyric acid bacteria living bacterium to fill the stomach daily;E,NEC model group,established the model and give 20 mg/g duplex butyric acid bacteria living bacterium to fill the stomach daily;Weighed their body weights and recorded everyday.Three days later,to fast one day.Put all the newborn mice to death.Anatomy all the rats and detect the contents of TNF-α and contrast them,observe the changes of their intestinal tissue and compared them;Observe the pathological changes of the intestinal tissue with HE staining. Results The average changes of body weight were A>D>E>C>B.There was no significance between group D and group E and no significance between group B and group C.Statistical significance existed among other groups.The mean scores of their HE staining pathology were B>D>C>E>A,there was statistical significance between A and other groups only.The averages of their TNF-α were group B>group C>group D>group E>group A.Based on the analysis of the above data,there was no significance between group D and group E and no significance between group B and group C.Statistical significance existed among other groups. Conclusion The optimal dose of duplex butyric acid bacteria living bacterium in neonatal necrotizing enterocolitis mice model may be 4 to 20 mg/g.The equivalent dose of bifidobacterium is 4×103 CFU to 20×103CFU.
关键词
坏死性小肠结肠炎 /
双歧杆菌 /
剂量 /
新生鼠
Key words
neonatal necrotizing enterocolitis /
bifidobacterium /
dose /
newborn rats
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参考文献
[1] Thyoka M,de Coppi P,Eaton S,et al.Advanced necrotizing enterocolitis part 1:mortality[J].Eur J Pediatr Surg,2012,22(1):8-12.
[2] Murgas Torrazza R,Li N,Young C,et al.Pilot study using proteomics to identify predictive biomarkers of necrotizing enterocolitis from buccal swabs in very low birth weight infants[J].Neonatology,2013,104(3):234-242.
[3] Kastenberg ZJ,Sylvester KG.The surgical management of necrotizing enterocolitis[J].Clin Perinatol,2013,40(1):135-148.
[4] Rowland KJ,Choi PM,Warner BW.Role of growth factors in intestinal regeneration and repair in necrotizing enteroeolitis[J].Seminars in Pediatric Surgery,2013,22(2):101-111.
[5] 茹彩旺,吴福根,秦涛,等.双歧杆菌预防早产儿坏死性小肠结肠炎的疗效观察阴[J].中国微生态学杂志,2013,25(1):45-47.
[6] Tran L,Ferris M,Norori J,et a1.Necrotizing enterocolitis and cytomegalovirus infection in a premature infant[J].Pediatrics,2013,131(1):e318-e322.
[7] De Plaen IG.Inflammatory signaling in neerotizing enterocolitis[J].Clinicsin Perinatology,2013,40(1):109-124.
[8] 易小莲,张阿宏,严彩霞,等.新牛儿坏死性小肠结肠炎发病机制研究进展[J].中国新生儿科杂志,2011,26(2):130-132.
[9] Neu J,Walker WA.Necrotizing enterocolitis[J].N Engl J Med,2011,364(3):255-264.
[10] Sheng Q,Lv z,Cai W,et al.Protective effects of hydrogenrich saline on necrotizing enterocolitis in neonatal rats[J].J Pediatr Surg,2013,48(8):1697-1706.
[11] Bhatia AM,Stoll BJ,Cismowski MJ,et al.Cytokine levels in the preterrn infant with neonatal intestinal injury[J].Am J Perinatol,2013,31(6):489-496.
[12] Hogberg N,Stenback A,Carlsson PO,et al.Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis[J].J Pediatr Surg,2013,48(11):2308-2312.
[13] Manzoni P,Lista G,Gallo E,et al.Routine Lactobacillus rhamnosus GG administration in VLBW infants:a retrospective,6-year cohort study[J].Early Hum Dev,2011,87:s35-38.
[14] Deshpande GC,Rao SC,Keil AD,et al.Evidence-based guidelines for use of probioties in preterm neonates[J].BMC Med,2011,9:92-104.
[15] Mirpuri J,Sotnikov I,Myers L,et al.Lactobaeillus rhamnosus(LGG)regulates IL-10 signaling in the developing mufine colon through up regulation of the IL-10R2 receptor subunit[J].PLoS One,2012,7:51-55.
[16] Zhou W,Li W,Zheng XH,et al.Glutamine downregulates TLR-2 and TLR-4 expression and protects intestinal tract in preterm neonatal rats with neerotizing enterocolitis[J].J Pediatr Surg,2014,49:1057-1063.
[17] Lu P,Sodhi CP,Jia H,et al.Animal models of gastrointestinal and liver diseases.Animal models of necrotizing enterocolitis:pathophysiology,translational relevance,and challenges[J].Am J Physiol Gastrointest Liver Physiol,2014,306:G917-928.
[18] 吴文燊,王艳丽,温婉文,等.双歧杆菌对新生大鼠坏死性小肠结肠炎模型的保护作用[J].中国新生儿科杂志,2016,31(3):212-216.
[19] 苏衡,吕回,周伟,等.双歧杆菌对坏死性小肠结肠炎新生大鼠肠道保护作用的机制[J].中华围产医学杂志,2015,18(4):290-295.
[20] 李美雪,周伟,吕回,等.脂多糖联合人工喂养诱导新生大鼠坏死性小肠结肠炎模型的建立与评价[J].发育医学电子杂志,2014,2(1):21-27.
[21] 富琴琴,林梅芳,邓庆先,等.谷氨酰胺对新生大鼠坏死性小肠结肠炎肠道组织Caspase3及增殖细胞核抗原表达的影响[J].中国新生儿科杂志,2016,31(2):139-144.