肺表面活性物质的成分和功能研究现状
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摘要
肺表面活性物质(PS)已经被临床常规应用于临床治疗新生儿呼吸窘迫综合征(NRDS)。PS是由脂类和各种肺表面蛋白(SP)构成的复合物。近年基础和临床研究对PS的组成成分及其功能具有更深入的认识。PS复杂的脂质成分塑造了其独特的物理属性。SP-A、-D不仅是PS的成分,还分布于肺外组织,可防御各种病原体,并且具有维持免疫稳态的作用。各种PS天然制剂在成分和性质上均存在差异,这也使其对NRDS患儿的治疗疗效、预后等各异,但是哪种PS天然制剂更具有优势,则迄今尚无定论。为了避免PS天然制剂可能导致的传染性疾病发生风险与免疫排斥反应风险及降低药物的经济成本,PS人工制剂的研发已成为热点。目前有关PS成分及其功能的研究多聚焦于SP-B、-C及其在NRDS发病机制中的作用,而本研究涉及过去少有关注的PS脂质成分与其他SP组成。笔者拟对PS的成分和功能进行全面、详实论述,同时介绍最新PS人工合成制剂,旨在为PS治疗NRDS患儿的临床应用提供新认识。
Pulmonary surfactant(PS) has been routinely used to treat neonatal respiratory distress syndrome(NRDS). PS is a complex composed of lipids and various surfactant protein(SP). In recent years, basic and clinical studies have gained a deeper understanding of the composition of PS and the function of each component. The complex lipid composition of PS shapes its unique physical properties. SP-A and SP-D are not only the components of PS, but also distribute in the extrapulmonary tissues to defend against various pathogens and maintain the immune homeostasis. There are differences in the composition and properties of various kinds of natural preparations of PS, which results in different manifestations in terms of the efficacy and prognosis of NRDS patients. However, there is still no conclusion as to which natural preparation of PS has more advantages. In order to avoid the infection risk and immune rejection reactions risk of PS natural preparations and reduce the economic cost of drugs, the research and development of PS artificial preparations have become a hot spot. At present, studies on the composition and function of PS mostly focus on SP-B and SP-C and their roles in the pathogenesis of NRDS. This study involves PS lipid components and other types of SP, which have received little attention before. The composition and function of PS are comprehensively and fully discussed. At the same time, the latest PS artificial preparations are introduced, which provides a new understanding for the clinical application of PS in treating NRDS infants.
Pulmonary surfactant(PS) has been routinely used to treat neonatal respiratory distress syndrome(NRDS). PS is a complex composed of lipids and various surfactant protein(SP). In recent years, basic and clinical studies have gained a deeper understanding of the composition of PS and the function of each component. The complex lipid composition of PS shapes its unique physical properties. SP-A and SP-D are not only the components of PS, but also distribute in the extrapulmonary tissues to defend against various pathogens and maintain the immune homeostasis. There are differences in the composition and properties of various kinds of natural preparations of PS, which results in different manifestations in terms of the efficacy and prognosis of NRDS patients. However, there is still no conclusion as to which natural preparation of PS has more advantages. In order to avoid the infection risk and immune rejection reactions risk of PS natural preparations and reduce the economic cost of drugs, the research and development of PS artificial preparations have become a hot spot. At present, studies on the composition and function of PS mostly focus on SP-B and SP-C and their roles in the pathogenesis of NRDS. This study involves PS lipid components and other types of SP, which have received little attention before. The composition and function of PS are comprehensively and fully discussed. At the same time, the latest PS artificial preparations are introduced, which provides a new understanding for the clinical application of PS in treating NRDS infants.
引文
[1] Olmeda B, Martinez-Calle M, Pérez-Gil J. Pulmonary surfactant metabolism in the alveolar airspace: biogenesis, extracellular conversions, recycling[J]. Ann Anat, 2016, 209: 78-92.
[2] Parra E, Pérez-Gil J. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films[J]. Chem Phys Lipids, 2015, 185(1): 153-175.
[3] Zhang H, Fan Q, Wang YE, et al. Comparative study of clinical pulmonary surfactants using atomic force microscopy[J]. Biochim Biophys Acta, 2011, 1808(7): 1832-1842.
[4] Kim K, Choi SQ, Zell ZA, et al. Effect of cholesterol nanodomains on monolayer morphology and dynamics[J]. Proc Natl Acad Sci USA, 2013, 110(33): E3054-E3060.
[5] Sardesai S, Biniwale M, Wertheimer F, et al. Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future[J]. Pediatr Res, 2017, 81(1-2): 240-248.
[6] Whitsett JA. The molecular era of surfactant biology[J]. Neonatology, 2014, 105(4): 337-343.
[7] Lopez-Rodriguez E, Pérez-Gil J. Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy[J]. Biochim Biophys Acta, 2014, 1838(6): 1568-1585.
[8] Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease[J]. Annu Rev Physiol, 2004, 66: 601-623.
[9] Mayer S, Raulf MK, Lepenies B. C-type lectins: their network and roles in pathogen recognition and immunity[J]. Histochem Cell Biol, 2017, 147(2): 223-237.
[10] Vieira F, Kung JW, Bhatti F. Structure, genetics and function of the pulmonary associated surfactant proteins A and D: the extra-pulmonary role of these C type lectins[J]. Ann Anat, 2017, 211: 184-201.
[11] Ujma S, Horsnell WGC, Katz AA, et al. Non-pulmonary immune functions of surfactant proteins A and D [J]. J Innate Immun, 2017, 9(1): 3-11.
[12] Jakel A, Qaseem AS, Kishore U, et al. Ligands and receptors of lung surfactant proteins SP-A and SP-D[J]. Front Biosci (Landmark Ed), 2013, 18(3): 1129-1140.
[13] Hsieh IN, De Luna X, White MR, et al. The role and molecular mechanism of action of surfactant protein D in innate host defense against influenza A virus[J]. Front Immunol, 2018, 9(6): 1368-1376.
[14] El Saleeby CM, Li R, Somes GW, et al. Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population[J]. J Pediatr, 2010, 156(3): 409-414.
[15] Levine AM, Elliott J, Whitsett JA, et al. Surfactant protein-D enhances phagocytosis and pulmonary clearance of respiratory syncytial virus[J]. Am J Respir Cell Mol Biol, 2004, 31(2): 193-199.
[16] Yang HY, Li H, Wang YG, et al. Correlation analysis between single nucleotide polymorphisms of pulmonary surfactant protein A gene and pulmonary tuberculosis in the Han population in China[J]. Int J Infect Dis, 2014, 26: 31-36.
[17] Hsieh MH, Ou CY, Hsieh WY, et al. Functional analysis of genetic variations in surfactant protein D in mycobacterial infection and their association with tuberculosis[J]. Frontin Immunol, 2018, 9: 1543-1553.
[18] Wong SWW, Rani M, Dodagatta-Marri E, et al. Fungal melanin stimulates surfactant protein D-mediated opsonization of and host immune response to Aspergillus fumigatus spores[J]. J Biol Chem, 2018, 293(13): 4901-4912.
[19] Reinhardt A, Wehle M, Geissner A, et al. Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures[J]. J Struct Biol, 2016, 195(3): 387-395.
[20] Qadi M, Lopezcausapé C, Izquierdorabassa S, et al. Surfactant protein A recognizes outer membrane protein OprH on Pseudomonas aeruginosa chronic infection isolates[J]. J Infect Dis, 2016, 214(9): 1449-1455.
[21] Thawer S, Auret J, Schnoeller C, et al. Surfactant protein-D is essential for immunity to helminth infection[J]. PLoS Pathog, 2016, 12(2): e1005461.
[22] Tan RM, Kuang Z, Hao Y, et al. Type Ⅳ pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A[J]. Infect Immun, 2015, 83(4): 1339-1346.
[23] Clark HW, Mackay RM, Deadman ME, et al. Crystal structure of a complex of surfactant protein D and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D resistant strains[J]. Infect Immun, 2016, 84(5): 1585-1592.
[24] Gardai SJ, Xiao YQ, Dickinson M, et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation[J]. Cell, 2003, 115(1): 13-23.
[25] Mackay RM, Grainge CL, Lau LC, et al. Airway surfactant protein D deficiency in adults with severe asthma[J]. Chest, 2016, 149(5): 1165-1172.
[26] Yang X, Yan J, Feng J. Surfactant protein A is expressed in the central nervous system of rats with experimental autoimmune encephalomyelitis, and suppresses inflammation in human astrocytes and microglia[J]. Mol Med Rep, 2017, 15(6): 3555-3565.
[27] Sarashina-Kida H, Negishi H, Nishio J, et al. Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis[J]. Proc Natl Acad Sci USA, 2017, 114(38): 10178-10183.
[28] Luo JM, Liu ZQ, Eugene CY. Overexpression of pulmonary surfactant protein A like molecules in inflammatory bowel disease tissues[J]. J Cent South Univ (Med Sci), 2008, 33(11): 979-986.
[29] Rokade S, Kishore U, Madan T. Surfactant protein D regulates murine testicular immune milieu and sperm functions[J]. Am J Reprod Immunol, 2017, 77(3): e12629.
[30] Madhukaran SP, Kishore U, Jamil K, et al. Decidual expression and localization of human surfactant protein SP-A and SP-D, and complement protein C1q[J]. Mol Immunol, 2015, 66(2): 197-207.
[31] Wu X, Zhao G, Lin J, et al. The production mechanism and immunosuppression effect of pulmonary surfactant protein D via toll like receptor 4 signaling pathway in human corneal epithelial cells during Aspergillus fumigatus infection[J]. Int Immunopharmacol, 2015, 29(2): 433-439.
[32] Zhang Z, Abdel-Razek O, Hawgood S, et al. Protective role of surfactant protein D in ocular Staphylococcus aureus infection[J]. PLoS One, 2015, 10(9): e0138597.
[33] Schicht M, Knipping S, Hirt R, et al. Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps[J]. Am J Rhinol Allergy, 2013, 27(1): 24-29.
[34] Uhliarova B, Kopincova J, Adamkov M, et al. Surfactant proteins A and D are related to severity of the disease, pathogenic bacteria and comorbidity in patients with chronic rhinosinusitis with and without nasal polyps[J]. Clin Otolaryngol, 2016, 41(3): 249-258.
[35] Benkoe T, Baumann S, Weninger M, et al. Comprehensive evaluation of 11 cytokines in premature infants with surgical necrotizing enterocolitis[J]. PLoS One, 2013, 8(3): e58720.
[36] Benkoe T, Reck C, Gleiss A, et al. Interleukin 8 correlates with intestinal involvement in surgically treated infants with necrotizing enterocolitis[J]. J Pediatr Surg, 2012, 47(8): 1548-1554.
[37] Saka R, Wakimoto T, Nishiumi F, et al. Surfactant protein-D attenuates the lipopolysaccharide-induced inflammation in human intestinal cells overexpressing toll-like receptor 4[J]. Pediatr Surg Int, 2016, 32(1): 59-63.
[38] Quintanilla HD, Liu Y, Fatheree NY, et al. Oral administration of surfactant protein-a reduces pathology in an experimental model of necrotizing enterocolitis[J]. J Pediatr Gastroenterol Nutr, 2015, 60(5): 613-620.
[39] Rausch F, Schicht M, Paulsen F, et al. "SP-G", a putative new surfactant protein--tissue localization and 3D structure[J]. PLoS One, 2012, 7(10): e47789.
[40] Schicht M, Rausch F, Finotto S, et al. SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation[J]. Eur Respir J, 2014, 44(2): 447-456.
[41] Merritt TA, Hallman M, Bloom BT, et al. Prophylactic treatment of very premature infants with human surfactant[J]. N Engl J Med, 1986, 315(13): 785-790.
[42] Vaucher YE, Harker L, Merritt TA, et al. Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: a randomized, placebo-controlled trial of human surfactant[J]. J Pediatr, 1993, 122(1): 126-132.
[43] Halliday HL. Surfactants: past, present and future[J]. J Perinatol, 2008, 28(Suppl 1): S47-S56.
[44] Hermans E, Bhamla MS, Kao P, et al. Lung surfactants and different contributions to thin film stability[J]. Soft Matter, 2015, 11(41): 8048-8057.
[45] Singh N, Halliday HL, Stevens TP, et al. Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants[J]. Cochrane Database Syst Rev, 2015, 12: CD010249.
[46] Curstedt T, Calkovska A, Johansson J. New generation synthetic surfactants[J]. Neonatology, 2013, 103(4): 327-330.
[47] Soll RF, Blanco F. Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome[J]. Cochrane Database Syst Rev, 2001, 2: CD000144.
[48] Seehase M, Collins JJ, Kuypers E, et al. New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs[J]. PLoS One, 2012, 7(10): e47631.
[49] Ricci F, Murgia X, Razzetti R, et al. In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633[J]. Pediatr Res, 2017, 81(2): 369-375.
[50] Sweet DG, Turner MA, Straňák Z, et al. A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome[J]. Arch Dis Child Fetal Neonatal Ed, 2017, 102(6): F497-F503.
[51] Rey-Santano C, Mielgo VE, Murgia X, et al. Cerebral and lung effects of a new generation synthetic surfactant with SP-B and SP-C analogs in preterm lambs[J]. Pediatr Pulmonol, 2017, 52(7): 929-938.
[52] Veldhuizen R, Nag K, Orgeig S, et al. The role of lipids in pulmonary surfactant[J]. Biochim Biophys Acta, 1998, 1408(2-3): 90-108.
[53] Brogden KA. Changes in pulmonary surfactant during bacterial pneumonia[J]. Ant Van Leeuwenhoek, 1991, 59(4): 215-223.
[54] Suri LN, Cruz A, Veldhuizen RA, et al. Adaptations to hibernation in lung surfactant composition of 13-lined ground squirrels influence surfactant lipid phase segregation properties[J]. Biochim Et Biophys Acta, 2013, 1828(8):1707-1714.
[2] Parra E, Pérez-Gil J. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films[J]. Chem Phys Lipids, 2015, 185(1): 153-175.
[3] Zhang H, Fan Q, Wang YE, et al. Comparative study of clinical pulmonary surfactants using atomic force microscopy[J]. Biochim Biophys Acta, 2011, 1808(7): 1832-1842.
[4] Kim K, Choi SQ, Zell ZA, et al. Effect of cholesterol nanodomains on monolayer morphology and dynamics[J]. Proc Natl Acad Sci USA, 2013, 110(33): E3054-E3060.
[5] Sardesai S, Biniwale M, Wertheimer F, et al. Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future[J]. Pediatr Res, 2017, 81(1-2): 240-248.
[6] Whitsett JA. The molecular era of surfactant biology[J]. Neonatology, 2014, 105(4): 337-343.
[7] Lopez-Rodriguez E, Pérez-Gil J. Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy[J]. Biochim Biophys Acta, 2014, 1838(6): 1568-1585.
[8] Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease[J]. Annu Rev Physiol, 2004, 66: 601-623.
[9] Mayer S, Raulf MK, Lepenies B. C-type lectins: their network and roles in pathogen recognition and immunity[J]. Histochem Cell Biol, 2017, 147(2): 223-237.
[10] Vieira F, Kung JW, Bhatti F. Structure, genetics and function of the pulmonary associated surfactant proteins A and D: the extra-pulmonary role of these C type lectins[J]. Ann Anat, 2017, 211: 184-201.
[11] Ujma S, Horsnell WGC, Katz AA, et al. Non-pulmonary immune functions of surfactant proteins A and D [J]. J Innate Immun, 2017, 9(1): 3-11.
[12] Jakel A, Qaseem AS, Kishore U, et al. Ligands and receptors of lung surfactant proteins SP-A and SP-D[J]. Front Biosci (Landmark Ed), 2013, 18(3): 1129-1140.
[13] Hsieh IN, De Luna X, White MR, et al. The role and molecular mechanism of action of surfactant protein D in innate host defense against influenza A virus[J]. Front Immunol, 2018, 9(6): 1368-1376.
[14] El Saleeby CM, Li R, Somes GW, et al. Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population[J]. J Pediatr, 2010, 156(3): 409-414.
[15] Levine AM, Elliott J, Whitsett JA, et al. Surfactant protein-D enhances phagocytosis and pulmonary clearance of respiratory syncytial virus[J]. Am J Respir Cell Mol Biol, 2004, 31(2): 193-199.
[16] Yang HY, Li H, Wang YG, et al. Correlation analysis between single nucleotide polymorphisms of pulmonary surfactant protein A gene and pulmonary tuberculosis in the Han population in China[J]. Int J Infect Dis, 2014, 26: 31-36.
[17] Hsieh MH, Ou CY, Hsieh WY, et al. Functional analysis of genetic variations in surfactant protein D in mycobacterial infection and their association with tuberculosis[J]. Frontin Immunol, 2018, 9: 1543-1553.
[18] Wong SWW, Rani M, Dodagatta-Marri E, et al. Fungal melanin stimulates surfactant protein D-mediated opsonization of and host immune response to Aspergillus fumigatus spores[J]. J Biol Chem, 2018, 293(13): 4901-4912.
[19] Reinhardt A, Wehle M, Geissner A, et al. Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures[J]. J Struct Biol, 2016, 195(3): 387-395.
[20] Qadi M, Lopezcausapé C, Izquierdorabassa S, et al. Surfactant protein A recognizes outer membrane protein OprH on Pseudomonas aeruginosa chronic infection isolates[J]. J Infect Dis, 2016, 214(9): 1449-1455.
[21] Thawer S, Auret J, Schnoeller C, et al. Surfactant protein-D is essential for immunity to helminth infection[J]. PLoS Pathog, 2016, 12(2): e1005461.
[22] Tan RM, Kuang Z, Hao Y, et al. Type Ⅳ pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A[J]. Infect Immun, 2015, 83(4): 1339-1346.
[23] Clark HW, Mackay RM, Deadman ME, et al. Crystal structure of a complex of surfactant protein D and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D resistant strains[J]. Infect Immun, 2016, 84(5): 1585-1592.
[24] Gardai SJ, Xiao YQ, Dickinson M, et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation[J]. Cell, 2003, 115(1): 13-23.
[25] Mackay RM, Grainge CL, Lau LC, et al. Airway surfactant protein D deficiency in adults with severe asthma[J]. Chest, 2016, 149(5): 1165-1172.
[26] Yang X, Yan J, Feng J. Surfactant protein A is expressed in the central nervous system of rats with experimental autoimmune encephalomyelitis, and suppresses inflammation in human astrocytes and microglia[J]. Mol Med Rep, 2017, 15(6): 3555-3565.
[27] Sarashina-Kida H, Negishi H, Nishio J, et al. Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis[J]. Proc Natl Acad Sci USA, 2017, 114(38): 10178-10183.
[28] Luo JM, Liu ZQ, Eugene CY. Overexpression of pulmonary surfactant protein A like molecules in inflammatory bowel disease tissues[J]. J Cent South Univ (Med Sci), 2008, 33(11): 979-986.
[29] Rokade S, Kishore U, Madan T. Surfactant protein D regulates murine testicular immune milieu and sperm functions[J]. Am J Reprod Immunol, 2017, 77(3): e12629.
[30] Madhukaran SP, Kishore U, Jamil K, et al. Decidual expression and localization of human surfactant protein SP-A and SP-D, and complement protein C1q[J]. Mol Immunol, 2015, 66(2): 197-207.
[31] Wu X, Zhao G, Lin J, et al. The production mechanism and immunosuppression effect of pulmonary surfactant protein D via toll like receptor 4 signaling pathway in human corneal epithelial cells during Aspergillus fumigatus infection[J]. Int Immunopharmacol, 2015, 29(2): 433-439.
[32] Zhang Z, Abdel-Razek O, Hawgood S, et al. Protective role of surfactant protein D in ocular Staphylococcus aureus infection[J]. PLoS One, 2015, 10(9): e0138597.
[33] Schicht M, Knipping S, Hirt R, et al. Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps[J]. Am J Rhinol Allergy, 2013, 27(1): 24-29.
[34] Uhliarova B, Kopincova J, Adamkov M, et al. Surfactant proteins A and D are related to severity of the disease, pathogenic bacteria and comorbidity in patients with chronic rhinosinusitis with and without nasal polyps[J]. Clin Otolaryngol, 2016, 41(3): 249-258.
[35] Benkoe T, Baumann S, Weninger M, et al. Comprehensive evaluation of 11 cytokines in premature infants with surgical necrotizing enterocolitis[J]. PLoS One, 2013, 8(3): e58720.
[36] Benkoe T, Reck C, Gleiss A, et al. Interleukin 8 correlates with intestinal involvement in surgically treated infants with necrotizing enterocolitis[J]. J Pediatr Surg, 2012, 47(8): 1548-1554.
[37] Saka R, Wakimoto T, Nishiumi F, et al. Surfactant protein-D attenuates the lipopolysaccharide-induced inflammation in human intestinal cells overexpressing toll-like receptor 4[J]. Pediatr Surg Int, 2016, 32(1): 59-63.
[38] Quintanilla HD, Liu Y, Fatheree NY, et al. Oral administration of surfactant protein-a reduces pathology in an experimental model of necrotizing enterocolitis[J]. J Pediatr Gastroenterol Nutr, 2015, 60(5): 613-620.
[39] Rausch F, Schicht M, Paulsen F, et al. "SP-G", a putative new surfactant protein--tissue localization and 3D structure[J]. PLoS One, 2012, 7(10): e47789.
[40] Schicht M, Rausch F, Finotto S, et al. SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation[J]. Eur Respir J, 2014, 44(2): 447-456.
[41] Merritt TA, Hallman M, Bloom BT, et al. Prophylactic treatment of very premature infants with human surfactant[J]. N Engl J Med, 1986, 315(13): 785-790.
[42] Vaucher YE, Harker L, Merritt TA, et al. Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: a randomized, placebo-controlled trial of human surfactant[J]. J Pediatr, 1993, 122(1): 126-132.
[43] Halliday HL. Surfactants: past, present and future[J]. J Perinatol, 2008, 28(Suppl 1): S47-S56.
[44] Hermans E, Bhamla MS, Kao P, et al. Lung surfactants and different contributions to thin film stability[J]. Soft Matter, 2015, 11(41): 8048-8057.
[45] Singh N, Halliday HL, Stevens TP, et al. Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants[J]. Cochrane Database Syst Rev, 2015, 12: CD010249.
[46] Curstedt T, Calkovska A, Johansson J. New generation synthetic surfactants[J]. Neonatology, 2013, 103(4): 327-330.
[47] Soll RF, Blanco F. Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome[J]. Cochrane Database Syst Rev, 2001, 2: CD000144.
[48] Seehase M, Collins JJ, Kuypers E, et al. New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs[J]. PLoS One, 2012, 7(10): e47631.
[49] Ricci F, Murgia X, Razzetti R, et al. In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633[J]. Pediatr Res, 2017, 81(2): 369-375.
[50] Sweet DG, Turner MA, Straňák Z, et al. A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome[J]. Arch Dis Child Fetal Neonatal Ed, 2017, 102(6): F497-F503.
[51] Rey-Santano C, Mielgo VE, Murgia X, et al. Cerebral and lung effects of a new generation synthetic surfactant with SP-B and SP-C analogs in preterm lambs[J]. Pediatr Pulmonol, 2017, 52(7): 929-938.
[52] Veldhuizen R, Nag K, Orgeig S, et al. The role of lipids in pulmonary surfactant[J]. Biochim Biophys Acta, 1998, 1408(2-3): 90-108.
[53] Brogden KA. Changes in pulmonary surfactant during bacterial pneumonia[J]. Ant Van Leeuwenhoek, 1991, 59(4): 215-223.
[54] Suri LN, Cruz A, Veldhuizen RA, et al. Adaptations to hibernation in lung surfactant composition of 13-lined ground squirrels influence surfactant lipid phase segregation properties[J]. Biochim Et Biophys Acta, 2013, 1828(8):1707-1714.