1.Comparison of the effect of ambroxol and dexamethasone on the expression of pulmonary surfactant proteins in the fetal rat lungs.
Xue-ming FU ; Jia-lin YU ; Guan-xin LIU ; Bing DENG
Chinese Journal of Pediatrics 2004;42(6):450-453
<b>OBJECTIVEb>To investigate the effects of maternally administered dexamethasone and ambroxol on the mRNA levels of surfactant proteins (SP-A, SP-B and SP-C) expression in fetal rat lungs at gestational age day 19.
<b>METHODSb>A 19-day fetal rat lung model was employed. In situ hybridization was used to detect the expression of SP-B mRNA in alveolar type II cell, and the levels of SP-A, SP-B and SP-C mRNAs were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
<b>RESULTSb>(1) SP-B mRNA was detected in situ in alveolar type II cells in fetal rat lung of day 19 gestational age; (2) In the late developmental period of fetal rat lungs, alveolar type II cells were also found around bronchus; (3) Comparing to beta-actin mRNA, the relative values of SP-A, SP-B and SP-C mRNAs were 0.81 +/- 0.26, 0.97 +/- 0.20 and 0.88 +/- 0.11 in fetal lung in the control group. The relative values of mRNAs of SP-A, SP-B and SP-C to beta-actin were 1.04 +/- 0.16, 1.28 +/- 0.29, 1.09 +/- 0.25 in fetal lungs of the ambroxol injected rats, and were 1.08 +/- 0.25, 1.23 +/- 0.35, 1.21 +/- 0.25 in fetal lungs of the dexamethasone injected rats, respectively. Both ambroxol and dexamethasone-treated rats had significantly higher mRNA expression of surfactant proteins compared to the control saline injected animals (P < 0.05). (4) There were no significant differences between ambroxol and dexamethasone in the effects of increasing expressions of surfactant protein mRNAs (P > 0.05).
<b>CONCLUSIONb>Antepartum administration of both ambroxol and dexamethasone can significantly increase fetal lung SP-A, SP-B and SP-C mRNAs expression.
Ambroxol ; pharmacology ; Animals ; Dexamethasone ; pharmacology ; Expectorants ; pharmacology ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Glucocorticoids ; pharmacology ; Lung ; drug effects ; embryology ; metabolism ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction
2.Surfactant protein B 1580 polymorphism is associated with susceptibility to chronic obstructive pulmonary disease in Chinese Han population.
Ruicheng, HU ; Yongjian, XU ; Zhenxiang, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2004;24(3):216-8, 238
Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C-->T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, chi2 = 4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allele (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
Alleles
;
China/ethnology
;
Genetic Predisposition to Disease/*genetics
;
Genotype
;
Polymorphism, Genetic/*genetics
;
Pulmonary Disease, Chronic Obstructive/*genetics
;
Pulmonary Surfactant-Associated Protein B/*genetics
;
Pulmonary Surfactant-Associated Protein B/physiology
;
Smoking/genetics
3.Evaluation and management of inherited disorders of surfactant metabolism.
Chinese Medical Journal 2010;123(20):2943-2947
<b>OBJECTIVEb>To review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).
<b>DATA SOURCESb>Review of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.
<b>STUDY SELECTIONb>Key articles in the field, author's work.
<b>RESULTSb>Inherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,
<b>CONCLUSIONSb>Inherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.
ATP-Binding Cassette Transporters ; genetics ; Humans ; Infant, Newborn ; Lung Diseases ; diagnosis ; etiology ; therapy ; Lung Transplantation ; Mutation ; Pulmonary Surfactant-Associated Protein B ; deficiency ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism
4.Effect of intrauterine acute ischemic-hypoxia on the expression of lung SP-A and SP-B in neonatal rats.
Xu-xu CAI ; Yue DU ; Hong GAO ; Zhen-ze CUI ; Yu-kun HAN
Chinese Journal of Pediatrics 2003;41(3):208-211
<b>OBJECTIVEb>Neonatal asphyxia is one of the main causes for the acute respiratory distress syndrome (ARDS) in full-term newborns. Now it is believed that the reduced amount and abnormal function of pulmonary surfactant due to various causes is a major factor leading to acute lung injury. This study aimed at using an intrauterine acute ischemic-hypoxia rat model and investigating the effect of intrauterine acute ischemic-hypoxia on the expression of surfactant protein A (SP-A) and surfactant protein B (SP-B) in neonatal rat lungs.
<b>METHODSb>The rat model of acute intrauterine ischemic-hypoxia was established by ligating the unilateral uterine horn vessels of Wistar rats at the 21st gestational day. While the rat pups from the other side of the uterus, of which the uterine horn vessel was not ligated, were the sham-operation group. Rat pups were delivered by cesarean section at the 20, 30 and 40 min following the ischemic-hypoxia insult. The rat pups delivered by cesarean section from the gestation of 21 days were the normal control group. There were 42 rat pups and 6 pups in each group in this study. The distribution of SP-B protein in the neonatal rat lungs of different period of ischemia was examined by using SABC method. The average gray value of SP-B staining in type II alveolar epithelial cells were measured by Universal Imaging Porporation with Meta Morph software. The reverse transcription polymerase chain reaction (RT-PCR) was performed to quantitate the expression of SP-A and SP-B mRNA.
<b>RESULTSb>Following the intrauterine acute ischemic-hypoxia, the numbers of type II alveolar epithelial cells with the positive SP-B staining were markedly declined. The average gray values at the 20, 30 and 40 min after the ischemia were 78.89 +/- 1.08, 79.69 +/- 0.13 and 80.00 +/- 0.63, respectively, which increased significantly compared with the normal control group (76.13 +/- 0.43, P < 0.01). The expression of SP-A and SP-B mRNA was weak following the ischemic-hypoxia insult. The relative amounts of SP-A (1.16 +/- 0.06, 1.14 +/- 0.01 and 1.13 +/- 0.04, respectively) and SP-B (0.81 +/- 0.02, 0.78 +/- 0.02 and 0.79 +/- 0.04, respectively) at the 20, 30 and 40 min after the ischemia were reduced significantly compared with controls (1.27 +/- 0.09 and 0.89 +/- 0.06, respectively, P < 0.05 and < 0.01) and reduced gradually following the prolongation of the insult. There were no significant differences (P > 0.05) between the normal and sham operation control groups on the expressions of SP-B protein as well as the SP-A and SP-B mRNA.
<b>CONCLUSIONb>The reduced synthesis of SP-B protein and the reduced expression of SP-A and SP-B mRNA might be caused by intrauterine acute ischemic-hypoxia, which may support theoretically the early application of pulmonary surfactant including SP-A and SP-B for treating the lung injuries of asphyxia in newborns.
Animals ; Animals, Newborn ; Female ; Gene Expression ; Hypoxia ; physiopathology ; Ischemia ; physiopathology ; Lung ; metabolism ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Uterus ; blood supply
5.Effect of epidermal growth factor and dexamethasone on fetal rat lung development.
Lian MA ; Ai-hong WANG ; Law FRIEDA ; Hong-yan HE ; Gui-xia MA ; Hong-wu WANG ; Li-min LIN
Chinese Medical Journal 2009;122(17):2013-2016
<b>BACKGROUNDb>Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis. We investigated the preventive and therapeutic effects of EGF in respiratory distress syndrome, by administering EGF and dexamethasone (Dex) to mother rat before delivery.
<b>METHODSb>Six female Sprague-Dawley (SD) rats were assigned to three groups (2 rats each); EGF or Dex was given to pregnant rats (EGF group and Dex group, respectively) from gestational day 16 to day 18 by intraperitoneal injection, while the group with normal saline injection was used as negative controls. Fetal rats were taken out of womb by hysterotomy on day 19 of pregnancy, then 24 fetal rats were randomly chosen from each group. Their body weights were measured, and pulmonary surfactant protein-A and -B (SP-A and SP-B) antigens were determined by immunohistochemical staining in each group. The histologic structure was examined under a light microscope, a light microscopic image system or an electron microscope.
<b>RESULTSb>The expressions of SP-A and SP-B could be detected in each group. A significant difference was observed for SP-A and SP-B in the EGF and Dex groups compared with the control group (P < 0.01). Image analysis showed that the relative values of air space area and interalveolar septa area in the EGF and Dex groups were significantly greater than those in the control group (P < 0.01), while no significant difference was found between the two groups (P > 0.05). The ultrastructural features of fetal lungs showed that the number of alveolar type II cells containing lamellar bodies in the EGF and Dex groups was apparently increased compared with that in the control group. The mean body weight of fetus from the Dex group was smaller than that from the control group ((1.3192 +/- 0.0533) g, (1.3863 +/- 0.0373) g), but there was no significant difference between the EGF group and the control group ((1.3986 +/- 0.0730) g, (1.3863 +/- 0.0373) g).
<b>CONCLUSIONSb>Maternal treatment with EGF and Dex on days 16 - 18 of gestation could promote morphogenesis and increase the surfactant levels in premature fetal lung. However, maternal treatment with Dex, not EGF, decreased the body weight.
Animals ; Dexamethasone ; pharmacology ; Epidermal Growth Factor ; pharmacology ; Female ; Immunohistochemistry ; Lung ; drug effects ; embryology ; ultrastructure ; Microscopy, Electron, Transmission ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Pulmonary Surfactant-Associated Protein B ; metabolism ; Rats ; Rats, Sprague-Dawley
6.Surfactant protein B expression and its role in the development of human fetal lung epithelial cells.
Xiang-yong KONG ; Jiang DU ; Zhi-chun FENG
Journal of Southern Medical University 2006;26(8):1154-1156
<b>OBJECTIVEb>To investigate the expression patterns of surfactant protein B (SP-B) and its role in the development of human fatal lung epithelial cells.
<b>METHODSb>Human fetal lung tissues were obtained from 37 fetuses of 10-34 weeks at abortion with parental consent and from two newborn infants who died of non-pulmonary causes. SP-B expression in the lung tissues was examined by immunohistochemistry.
<b>RESULTSb>SP-B was detected in the cytoplasm of nonciliated columnar epithelial cells of the human fetal lung in as early as the 16th week of gestation. The positive reaction of SP-B was enhanced during canalicular stages and was more intense in the distal than in the proximal airway epithelium. From the 25th week to the prenatal stage, SP-B expression underwent no significant changes in the primitive alveolar stage, but increased remarkably after birth.
<b>CONCLUSIONb>The expression and secretion of SP-B reflects the maturation of the epithelial cells in human fatal lungs, and may closely associate with the survival ability of the newborn infants.
Cell Survival ; physiology ; Cells, Cultured ; Epithelial Cells ; cytology ; metabolism ; Fetus ; Humans ; Infant, Newborn ; Lung ; Pulmonary Alveoli ; cytology ; metabolism ; Pulmonary Surfactant-Associated Protein B ; biosynthesis ; physiology
7.Surfactant protein B 1580 polymorphism is associated with susceptibility to chronic obstructive pulmonary disease in Chinese Han population.
Ruicheng HU ; Yongjian XU ; Zhenxiang ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2004;24(3):216-238
Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C-->T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, chi2 = 4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allele (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
Alleles
;
China
;
ethnology
;
Female
;
Genetic Predisposition to Disease
;
genetics
;
Genotype
;
Humans
;
Male
;
Polymorphism, Genetic
;
genetics
;
Pulmonary Disease, Chronic Obstructive
;
genetics
;
Pulmonary Surfactant-Associated Protein B
;
genetics
;
physiology
;
Smoking
;
genetics
8.Relationship between R236C site in exon 7 of SP-B gene and respiratory distress syndrome in Han newborns in western Inner Mongolia.
Jing WANG ; Hua MEI ; Chun-Zhi LIU ; Ya-Yu ZHANG ; Chun-Li LIU ; Dan SONG ; Yu-Heng ZHANG
Chinese Journal of Contemporary Pediatrics 2016;18(9):802-805
<b>OBJECTIVEb>To detect and analyze the genetic variation in exon 7 of lung surfactant protein B (SP-B), and to investigate the relationship between the genetic variation and the incidence of neonatal respiratory distress syndrome (NRDS) in Han populations in western Inner Mongolia.
<b>METHODSb>In the case-control study, 47 Han infants with NRDS were assigned to case group. All the 47 patients had the last three generations of their ancestors reside in western Inner Mongolia. Forty-seven Han newborns without NRDS were assigned to control group. PCR-based gene analysis was used to determine the mutation in exon 7 of SP-B gene and genotype and allele frequencies of the R236C site in exon 7 of SP-B gene.
<b>RESULTSb>In Han newborns in western Inner Mongolia, there was no mutation in exon 7 of SP-B gene; two genotypes, CC and CT, were identified in the R236C site in exon 7 of SP-B gene. No TT genotype was found in the two groups. There were no significant differences in the genotype frequency of CC or CT as well as the allele frequency of C or T between the case and control groups (CC: 72% vs 85%, P>0.05; CT: 28% vs 15%, P>0.05; C: 85% vs 93%, P>0.05; T: 15% vs 7%, P>0.05).
<b>CONCLUSIONSb>There is no mutation in exon 7 of SP-B gene in Han infants with NRDS in western Inner Mongolia. There is no significant association between the gene polymorphism of the R236C site in exon 7 of SP-B gene and the incidence of NRDS in Han populations in that region.
Case-Control Studies ; China ; Exons ; Female ; Genotype ; Humans ; Infant, Newborn ; Male ; Polymorphism, Genetic ; Pulmonary Surfactant-Associated Protein B ; genetics ; Respiratory Distress Syndrome, Newborn ; genetics
9.The changes in the pulmonary surface tension and the tissue content of surfactant substance protein B during early post-injury stage in rabbits inflicted with smoke inhalation injury.
Hua-Fei ZHENG ; Zhi-Yuan LIU ; Zong-Chen YANG
Chinese Journal of Burns 2004;20(3):141-144
<b>OBJECTIVEb>To investigate the changes in the pulmonary surface tension and the tissue content of surfactant substance protein B (SP-B) in rabbits during early post-injury stage after smoke inhalation injury.
<b>METHODSb>Thirty-two healthy rabbits inflicted with smoke inhalation injury were employed in the study as injury group, and they were sacrificed at 0.5, 2.0, 6.0, 12.0 post injury hours (PIH), with 8 rabbits at each time point. Another 8 rabbits were assigned to normal control group. The pulmonary tissue samples of the rabbits in each group were harvested for the collection of bronchial-alveolar lavage fluid (BALF). The changes in maximal tension (Tmax), minimal tension (Tmin) and hysteresis square (HS) of BALF were measured after the addition of 0.5, 1.0 and 3.0 ml of SP-B antibody into the BALF of the rabbits in each group. The changes in SP-B and SP-B mRNA contents in rabbit pulmonary tissue of each group were assessed with immunohistochemistry and in situ hybridization techniques, respectively.
<b>RESULTSb>There was no obvious difference in Tmax in BALF of each group or at each time point before and after the action of different concentrations of SP-B antibody in BALF (P > 0.05). But the Tmin in injury group at 2, 6 and 12 PIH was much higher than that before the addition of the antibody (P < 0.05). And the change in HS was similar to that in Tmin. The SP-B content in alveolar type II epithelial cells (AT-II) was decreased significantly at 2, 6 and 12 PIH, whereas the expression in SP-B mRNA exhibited no change.
<b>CONCLUSIONb>There was no obvious change in SP-B synthesis by AT-II in the lung tissue of the rabbits inflicted with smoke inhalation injury during early post injury stage. The increase of SP-B secretion from AT-II cells might be beneficial to the early protection of pulmonary tissue of the rabbits with smoke inhalation injury.
Animals ; Female ; Immunohistochemistry ; Lung ; chemistry ; Male ; Pulmonary Surfactant-Associated Protein B ; analysis ; genetics ; RNA, Messenger ; analysis ; Rabbits ; Smoke Inhalation Injury ; metabolism ; Surface Tension
10.Expression of lung surfactant proteins SP-B and SP-C and their modulating factors in fetal lung of FGR rats.
Fei-tao DENG ; Wei-xiang OUYANG ; Liang-fang GE ; Li ZHANG ; Xin-qun CHAI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2015;35(1):122-128
This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction (FGR). The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mRNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mRNA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.
Animals
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Base Sequence
;
DNA Primers
;
Female
;
Fetal Growth Retardation
;
Lung
;
embryology
;
metabolism
;
Peptides
;
metabolism
;
Pregnancy
;
Pulmonary Surfactant-Associated Protein B
;
metabolism
;
Rats
;
Real-Time Polymerase Chain Reaction