PDF(1432 KB)
PDF(1432 KB)
PDF(1432 KB)
支气管肺发育不良的动物模型造模方法及其评价
Methods for establishing animal model of bronchopulmonary dysplasia and their evaluation
随着新生儿救治水平的提高，早产儿尤其是极早早产儿和超低出生体重儿的存活率明显提高，导致支气管肺发育不良（BPD）的发病率逐年增加，BPD已成为早产儿，尤其是小早产儿最常见的呼吸系统疾病之一。肺泡发育受阻是导致BPD发生的重要原因，研究肺泡发育受阻机理及促进肺泡发育的干预措施是BPD研究的热点，选择合适的BPD动物模型是BPD基础研究获得有意义的研究结果的关键。基于此，本文总结及评价了几种常见的BPD动物模型造模方法及其产生的相应病理生理学改变，以期对BPD的发病机制、病理生理和防治对策的研究选择动物模型提供依据。
With the development of treatment, the survival rate of premature infants has significantly increased, especially extremely premature infants and very low birth weight infants. This has led to an increase in incidence of bronchopulmonary dysplasia (BPD) year by year. BPD has been one of the most common respiratory system diseases in premature infants, especially the small premature infants. Arrested alveolar development is an important cause of BPD. Therefore, the mechanism of arrested alveolar development and the intervention measures for promoting alveolar development are the focuses of research on BPD. Selecting the appropriate animal model of BPD is the key to obtaining meaningful results in the basic research on BPD. Based on above, several common methods for establishing an animal model of BPD and the corresponding changes in pathophysiology are summarized and evaluated in order to provide a reference for selecting the appropriate animal model in studies on the pathogenesis, pathophysiology, and prevention and control strategies of BPD.
Bronchopulmonary dysplasia / Modeling method / Evaluation / Premature infant
[1] 熊曾, 罗自强, 岳少杰. 对支气管肺发育不良从"经典型"向"新型"转变的思考[J]. 中华儿科杂志, 2014, 52(12):1-4.
[2] Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia[J]. N Engl J Med, 1967, 276(7):357-368.
[3] Latini G, De Felice C, Giannuzzi R, et al. Survival rate and prevalence of bronchopulmonary dysplasia in extremely low birth weight infants[J]. Early Hum Dev, 2013, 89(Suppl 1):S69-S73.
[4] Zysman-Colman Z, Tremblay GM, Bandeali S, et al. Bronchopulmonary dysplasia-trends over three decades[J]. Paediatr Child Health, 2013, 18(2):86-90.
[5] Carraro S, Filippone M, Da Dalt L, et al. Bronchopulmonary dysplasia:the earliest and perhaps the longest lasting obstructive lung disease in humans[J]. Early Hum Dev, 2013, 89(Suppl 3):S3-S5.
[6] Bhandari A, McGrath-Morrow S. Long-term pulmonary outcomes of patients with bronchopulmonary dysplasia[J]. Semin Perinatol, 2013, 37(2):132-137.
[7] Filippone M, Bonetto G, Corradi M, et al. Evidence of unexpected oxidative stress in airways of adolescents born very pre-term[J]. Eur Respir J, 2012, 40(5):1253-1259.
[8] Wang H, Gao X, Liu C, et al. Morbidity and mortality of neonatal respiratory failure in China:surfactant treatment in very immature infants[J]. Pediatrics, 2012, 129(3):e731-e740.
[9] Yang H, Fu J, Xue X, et al. Epithelial-mesenchymal transitions in bronchopulmonary dysplasia of newborn rats[J]. Pediatr Pulmonol, 2014, 49(11):1112-1123.
[10] Sun H, Choo-Wing R, Fan J, et al. Small molecular modulation of macrophage migration inhibitory factor in the hyperoxia-induced mouse model of bronchopulmonary dysplasia[J]. Respir Res, 2013, 14:27.
[11] Warner BB, Stuart LA, Papes RA, et al. Functional and pathological effects of prolonged hyperoxia in neonatal mice[J]. Am J Physiol, 1998, 275(1 Pt 1):L110-L117.
[12] Wang M, Luo Z, Liu S, et al. Glutamate mediates hyperoxia-induced newborn rat lung injury through N-methyl-D-aspartate receptors[J]. Am J Respir Cell Mol Biol, 2009, 40(3):260-267.
[13] Buczynski BW, Yee M, Paige Lawrence B, et al. Lung development and the host response to influenza A virus are altered by different doses of neonatal oxygen in mice[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 302(10):L1078-L1087.
[14] Sherman MP, Evans MJ, Campbell LA. Prevention of pulmonary alveolar macrophage proliferation in newborn rabbits by hyperoxia[J]. J Pediatr, 1988, 112(5):782-786.
[15] Galambos C, Sims-Lucas S, Abman SH. Histologic evidence of intrapulmonary anastomoses by three-dimensional reconstruction in severe bronchopulmonary dysplasia[J]. Ann Am Thorac Soc, 2013, 10(5):474-481.
[16] Hadchouel A, Franco-Montoya ML, Delacourt C. Altered lung development in bronchopulmonary dysplasia[J]. Birth Defects Res A Clin Mol Teratol, 2014, 100(3):158-167.
[17] Nold MF, Mangan NE, Rudloff I, et al. Interleukin-1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia[J]. Proc Natl Acad Sci U S A, 2013, 110(35):14384-14389.
[18] Wada K, Jobe AH, Ikegami M. Tidal volume effects on surfactant treatment responses with the initiation of ventilation in preterm lambs[J]. J Appl Physiol(1985), 1997, 83(4):1054-1061.
[19] Hillman NH, Moss TJ, Nitsos I, et al. Moderate tidal volumes and oxygen exposure during initiation of ventilation in preterm fetal sheep[J]. Pediatr Res, 2012, 72(6):593-599.
[20] Hillman NH, Kallapur SG, Jobe AH. Physiology of transition from intrauterine to extrauterine life[J]. Clin Perinatol, 2012, 39(4):769-783.
[21] Slutsky AS, Ranieri VM. Ventilator-induced lung injury[J]. N Engl J Med, 2013, 369(22):2126-2136.
[22] Ali Z, Schmidt P, Dodd J, et al. Bronchopulmonary dysplasia:a review[J]. Arch Gynecol Obstet, 2013, 288(2):325-333.
[23] 王伟, 蔡丽霞, 崔志瑞, 等. 早产大鼠宫内感染肺损伤时支气管肺泡灌洗液及肺组织中脂肪型脂肪酸结合蛋白的表达[J]. 郑州大学学报(医学版), 2015, 50(1):44-47.
[24] Kallapur SG, Presicce P, Senthamaraikannan P, et al. Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance[J]. J Immunol, 2013, 191(3):1102-1109.
[25] Wright CJ, Kirpalani H. Targeting inflammation to prevent bronchopulmonary dysplasia:can new insights be translated into therapies?[J]. Pediatrics, 2011, 128(1):111-126.
[26] Ambalavanan N, Nicola T, Hagood J, et al. Transforming growth factor-beta signaling mediates hypoxia-induced pulmonary arterial remodeling and inhibition of alveolar development in newborn mouse lung[J]. Am J Physiol Lung Cell Mol Physiol, 2008, 295(1):L86-L95.
[27] Olave N, Nicola T, Zhang W, et al. Transforming growth factor-β regulates endothelin-1 signaling in the newborn mouse lung during hypoxia exposure[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 302(9):L857-L865.
[28] Berger J, Bhandari V. Animal models of bronchopulmonary dysplasia. The term mouse models[J]. Am J Physiol Lung Cell Mol Physiol, 2014, 307(12):L936-L947.
[29] Huo H, Luo Z, Wang M, et al. MicroRNA expression profile in intrauterine hypoxia-induced pulmonary hypoplasia in rats[J]. Exp Ther Med, 2014, 8(3):747-753.
[30] 张爱民, 王娟梅, 方亦兵, 等. 宫内缺氧对新生大鼠肺血管发育及肺血管内皮生长因子表达的影响[J].中南大学学报(医学版), 2013, 38(11):1104-1109.
[31] Harding R, Maritz G. Maternal and fetal origins of lung disease in adulthood[J]. Semin Fetal Neonatal Med, 2012, 17(2):67-72.
[32] Ratner V, Slinko S, Utkina-Sosunova I, et al. Hypoxic stress exacerbates hyperoxia-induced lung injury in a neonatal mouse model of bronchopulmonary dysplasia[J]. Neonatology, 2009, 95(4):299-305.
[33] Gortner L, Monz D, Mildau C, et al. Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia:closer to clinical features?[J]. Ann Anat, 2013, 195(4):351-358.
[34] Monz D, Tutdibi E, Mildau C, et al. Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice[J]. PLoS One, 2013, 8(9):e74740.
[35] Bry K, Whitsett JA, Lappalainen U. IL-1beta disrupts postnatal lung morphogenesis in the mouse[J]. Am J Respir Cell Mol Biol, 2007, 36(1):32-42.
[36] Hogmalm A, Bäckström E, Bry M, et al. Role of CXC chemokine receptor-2 in a murine model of bronchopulmonary dysplasia[J]. Am J Respir Cell Mol Biol, 47(6):746-758.
[37] Aghai ZH, Saslow JG, Mody K, et al. IFN-γ and IP-10 in tracheal aspirates from premature infants:relationship with bronchopulmonary dysplasia[J]. Pediatr Pulmonol, 2013, 48(1):8-13.
[38] Harijith A, Choo-Wing R, Cataltepe S, et al. A role for matrix metalloproteinase 9 in IFNγ-mediated injury in developing lungs:relevance to bronchopulmonary dysplasia[J]. Am J Respir Cell Mol Biol, 2011, 44(5):621-630.
[39] Sun H, Choo-Wing R, Sureshbabu A, et al. A critical regulatory role for macrophage migration inhibitory factor in hyperoxia-induced injury in the developing murine lung[J]. PLoS One, 2013, 8(4):e60560.
国家自然科学基金（81500001）；国家自然科学基金（81370098）。
