Incomplete development of the lung secondary to extreme prematurity or pulmonary hypoplasia causes significant morbidity and mortality during the neonatal period. Currently, the management is primarily supportive with...Incomplete development of the lung secondary to extreme prematurity or pulmonary hypoplasia causes significant morbidity and mortality during the neonatal period. Currently, the management is primarily supportive with no specific treatment to stimulate the growth and development of the lung. Mechanical forces generated inside the fetal lung by constant distention pressure and "breathing-like movements" are a major determinant of fetal lung development. However, the mechanisms by which lung cells sense these mechanical signals to promote lung development are not well-defined. Tracheal ligation has been used not only experimentally but also in human fetuses affected by severe congenital diaphragmatic hernia to stimulate lung growth and decrease the degree of pulmonary hypoplasia. Past investigations suggested that the increase of intratracheal pressure after tracheal ligation releases soluble factors that are critical for lung development. Studies from our laboratory have shown that mechanical strain of fetal type Ⅱ epithelial cells, simulating mechanical forces in utero, promotes differentiation via release of epidermal growth factor receptor ligands heparin binding epidermal growth factor-like growth factor and transforming growth factor alpha. The identification of growth factors released by mechanical forces that are importantfor normal lung development could lead to novel treatments to accelerate lung development.展开更多
To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Con...To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF-Ⅰ, -Ⅱ (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF-Ⅰ in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-Ⅰ during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-Ⅰ was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-Ⅱ took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-Ⅱ in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-Ⅰ, -Ⅱ mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-Ⅰ, -Ⅱ and lung development in newborns. The IGF-Ⅱ works at early stage and the that of IGF-Ⅰ works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.展开更多
Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats ...Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and protein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.展开更多
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 est...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 m RNA 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 mR NA 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.展开更多
From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added ...From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.展开更多
This study investigated the expression of lung surfactant proteins (SP-B and SP-C),and regulatory factors [forkhead box A2(FOXA2)and nitrolyogenic FOXA2 (N-FOXA2)]in the fetal lung of rats with gestational diabetes me...This study investigated the expression of lung surfactant proteins (SP-B and SP-C),and regulatory factors [forkhead box A2(FOXA2)and nitrolyogenic FOXA2 (N-FOXA2)]in the fetal lung of rats with gestational diabetes mellitus (GDM)in order to study the mechanism of pulmonary dysplasia.The rat GDM model was established by using streptozotocin intraperitoneally in the first stage of pregnancy.There were 10 rats in the GDM group,and 10 healthy rats in normal control group without any treatment.Fetal lungs of two groups were taken at day 21 of pregnancy.Blood glucose levels of maternal rats and fetal rats were measured by Roche blood glucose meter.The histological changes in the fetal lung were observed under the light microscope in both groups.The SP-B,SP-C and FOXA2were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B,SP-C,total FOXA2,FOXA2 in nucleus (n-FOXA2), N-FOXA2 proteins were detected by Western blotting,and the relative expression levels of SP-B,SP-C,FOXA2 mRNA in the fetal lung of two groups were detected by RT-PCR.The results showed that blood glucose levels of maternal rats and fetal rats in GDM group were higher than those in control group.The light microscope revealed fetal lung development retardation in GDM group.The expression of SP-B and SP-C in GDM group was significantly reduced as compared with control group (P<0.05).As compared with control group,the n-FOXA2 expression was significantly decreased in the fetal lung tissue,and N-FOXA2 was significantly increased in control group (P<0.05),but there was no significant changes in the total FOXA2(P>0.05).It was concluded that GDM can cause fetal lung development and maturation disorders,and FOXA2 in fetal lung tissue decreases while nitrocellulose FOXA2 increases.展开更多
Smoking during pregnancy is a major source of fetal exposure to numerous harmful agents present in tobacco smoke. Lung development involves complex biochemical processes resulting in dramatic changes which continue ev...Smoking during pregnancy is a major source of fetal exposure to numerous harmful agents present in tobacco smoke. Lung development involves complex biochemical processes resulting in dramatic changes which continue even after birth. In addition to type I cells which form the blood-air barrier, type II alveolar epithelial (AE) cells have important and diverse functions related to immunological protection and stabilization of the alveolus through synthesis and secretion of the pulmonary surfactant. Apoptosis or programmed cells death is an important physiological process during lung embryogenesis and for the proper maintenance of homeostasis. Caspases are proteases that play important roles in regulating apoptosis. Caspase-3 is the key executioner caspase in the cascade of events leading to cell death by apoptosis. We explored the hypothesis that cigarette smoke extract (CSE) induces apoptosis in fetal rat lung type II AE cells by activation of caspase-3. To analyze these factors, isolated fetal rat lung type II AE cells were used. The cells were exposed to different concentrations of CSE (5%, 10% or 15%) (v/v) for 60 min. The results of the present study showed that CSE induced apoptosis in fetal rat lung type II AE cells with a significant increase (p 0.05) in caspase-3 activity and decrease in cell proliferation at CSE concentrations of 10% and 15% (v/v). These observations indicate that cigarette smoke extract induces apoptosis by activation of caspase-3 in fetal rat lung type II AE cells in a dose-dependent manner and may potentially alter the regulated development of the lung and the appearance of the surfactant-producing type II alveolar cells which are critical for the establishment of adequate gas exchange at birth.展开更多
This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were deve...This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were developed by using an unsupervised machine-learning approach.Children’s neurodevelopment,anthropometry,and respiratory outcomes in thefirst 6 years of life were assessed at different ages.In a subgroup of participants,we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs.We identified 6 FGTs:early decelerating,early decelerating with late catch-up growth,early accelerating,early accelerating with late medium growth,late decelerating,and late accelerating.The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development,mental development,intelligence quotient,and lung function and a lower risk of behaviour and respiratory problems.Compared with the optimal FGT,early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function,while early accelerating FGT was associated with more severe autistic symptoms,poor lung function,and increased risks of overweight/obesity.Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs,whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT.Thesefindings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism.The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease,but further research on related mechanisms is still needed.展开更多
Background 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 prev...Background 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. Methods 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. Results 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 [I 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). Conclusions 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. Chin Med J 2009; 122(17):2013-2016展开更多
To investigate whether treatment with retinoic acid (RA) could improve level of lung alveolarization and influence lung collagen in newborn rats exposed to hyperoxia, newborn Sprague-Dawley rats aged 2 days were ra...To investigate whether treatment with retinoic acid (RA) could improve level of lung alveolarization and influence lung collagen in newborn rats exposed to hyperoxia, newborn Sprague-Dawley rats aged 2 days were randomly assigned to 8 groups:(1) air, (2) O 2, (3) air+NS, (4) O 2+NS, (5) air+dex, (6) O 2+dex, (7) air+RA and (8) O 2+RA. Group 2, 4 6 and 8 were kept in chambers containing 85 % oxygen, the values were checked 3 times a day. The other 4 groups were exposed to room air. Level of alveolarization and lung collagen were analyzed at age of 14 or 21 days through radial alveolar counts, alveolar airspace measurements, type Ⅰ, Ⅲ collagen immunohistochemical methods (SP method) and image processing system. Transforming growth factor-β receptors and procollagen mRNA accumulation were examined at age of 14 days through immunohistochemical methods and in situ hybridization. Our results showed that radial alveolar counts were increased and distal airspace was enlarged in group 8. TypeⅠcollagen was markedly increased, and transforming growth factor-β receptors and procollagen mRNA were decreased by retinoic acid in bronchial epithelial cells, alveolar epithelial cells and alveolar intersitium. It is concluded that retinoic acid can partially reverse lung development arrest during exposure to hyperoxia by increasing lung collagen.展开更多
To evaluate the effects of Jinye Baidu Granule (金叶败毒颗粒, JYBDG), a traditional Chinese medicine compound prescription, on fetal growth and development with maternal active human cytomegalovirus infection. Meth...To evaluate the effects of Jinye Baidu Granule (金叶败毒颗粒, JYBDG), a traditional Chinese medicine compound prescription, on fetal growth and development with maternal active human cytomegalovirus infection. Methods: A prospective, randomized and controlled trial was adopted during January 1996 to June 2002. From the pregnant women with an abnormal pregnant history, 240 cases were screened to be infected by human cytomegalovirus (HCMV) by enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). They were assigned according to the random number table to two groups. The 122 cases in the treatment group were administrated with JYBDG, one package each time, three times a day for two continuous weeks, while the other 118 in the control group did not receive any treatment. The negative conversion rate of both HCMV-IgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate between the two groups were compared, and fetal growth and development in partial fetuses were also observed. Results: The negative conversion rate of both HCMV-IgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate in the treatment group were 77. 05% (94/122), 48.98% (48/98) and 21.74% (10/46) respectively, while those in the control group were 38. 14% (45/118), 67.50% (54/80) and 52.63% (20/38) respectively, all showing significant difference between the two groups (P〈0.01). Totally 35 normal infants and 11 abnormal infants were born in the treatment group, and the number in the control group was 20 and 18 respectively, and comparison between the two groups showed significant difference (P〈0.01). Six months of child birth, the scores of both mental development index (MDI) and psychomotor development index (PDI) of infants were higher in the treatment group (20 cases) than those in the control group (20 cases), but there was no significant difference between the two groups (P〉0.05). Conclusion: JYBDG could decrease the intrauterine transmission of HCMV and is beneficial to fetal growth and development.展开更多
基金Supported by National Institutes of Health,Grant R01 HD052670
文摘Incomplete development of the lung secondary to extreme prematurity or pulmonary hypoplasia causes significant morbidity and mortality during the neonatal period. Currently, the management is primarily supportive with no specific treatment to stimulate the growth and development of the lung. Mechanical forces generated inside the fetal lung by constant distention pressure and "breathing-like movements" are a major determinant of fetal lung development. However, the mechanisms by which lung cells sense these mechanical signals to promote lung development are not well-defined. Tracheal ligation has been used not only experimentally but also in human fetuses affected by severe congenital diaphragmatic hernia to stimulate lung growth and decrease the degree of pulmonary hypoplasia. Past investigations suggested that the increase of intratracheal pressure after tracheal ligation releases soluble factors that are critical for lung development. Studies from our laboratory have shown that mechanical strain of fetal type Ⅱ epithelial cells, simulating mechanical forces in utero, promotes differentiation via release of epidermal growth factor receptor ligands heparin binding epidermal growth factor-like growth factor and transforming growth factor alpha. The identification of growth factors released by mechanical forces that are importantfor normal lung development could lead to novel treatments to accelerate lung development.
文摘To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF-Ⅰ, -Ⅱ (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF-Ⅰ in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-Ⅰ during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-Ⅰ was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-Ⅱ took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-Ⅱ in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-Ⅰ, -Ⅱ mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-Ⅰ, -Ⅱ and lung development in newborns. The IGF-Ⅱ works at early stage and the that of IGF-Ⅰ works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.
文摘Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and protein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.
基金supported by the National Natural Science Foundation of China(No.30971072)
文摘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 m RNA 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 mR NA 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.
基金funded by the National Natural Science Foundation of China,No.81170577
文摘From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.
基金This work was supported by grants from the National Natural Science Foundation of China (No.30971072) and the Natural Science Foundation of Hubei Province (No.2017CFB749).
文摘This study investigated the expression of lung surfactant proteins (SP-B and SP-C),and regulatory factors [forkhead box A2(FOXA2)and nitrolyogenic FOXA2 (N-FOXA2)]in the fetal lung of rats with gestational diabetes mellitus (GDM)in order to study the mechanism of pulmonary dysplasia.The rat GDM model was established by using streptozotocin intraperitoneally in the first stage of pregnancy.There were 10 rats in the GDM group,and 10 healthy rats in normal control group without any treatment.Fetal lungs of two groups were taken at day 21 of pregnancy.Blood glucose levels of maternal rats and fetal rats were measured by Roche blood glucose meter.The histological changes in the fetal lung were observed under the light microscope in both groups.The SP-B,SP-C and FOXA2were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B,SP-C,total FOXA2,FOXA2 in nucleus (n-FOXA2), N-FOXA2 proteins were detected by Western blotting,and the relative expression levels of SP-B,SP-C,FOXA2 mRNA in the fetal lung of two groups were detected by RT-PCR.The results showed that blood glucose levels of maternal rats and fetal rats in GDM group were higher than those in control group.The light microscope revealed fetal lung development retardation in GDM group.The expression of SP-B and SP-C in GDM group was significantly reduced as compared with control group (P<0.05).As compared with control group,the n-FOXA2 expression was significantly decreased in the fetal lung tissue,and N-FOXA2 was significantly increased in control group (P<0.05),but there was no significant changes in the total FOXA2(P>0.05).It was concluded that GDM can cause fetal lung development and maturation disorders,and FOXA2 in fetal lung tissue decreases while nitrocellulose FOXA2 increases.
文摘Smoking during pregnancy is a major source of fetal exposure to numerous harmful agents present in tobacco smoke. Lung development involves complex biochemical processes resulting in dramatic changes which continue even after birth. In addition to type I cells which form the blood-air barrier, type II alveolar epithelial (AE) cells have important and diverse functions related to immunological protection and stabilization of the alveolus through synthesis and secretion of the pulmonary surfactant. Apoptosis or programmed cells death is an important physiological process during lung embryogenesis and for the proper maintenance of homeostasis. Caspases are proteases that play important roles in regulating apoptosis. Caspase-3 is the key executioner caspase in the cascade of events leading to cell death by apoptosis. We explored the hypothesis that cigarette smoke extract (CSE) induces apoptosis in fetal rat lung type II AE cells by activation of caspase-3. To analyze these factors, isolated fetal rat lung type II AE cells were used. The cells were exposed to different concentrations of CSE (5%, 10% or 15%) (v/v) for 60 min. The results of the present study showed that CSE induced apoptosis in fetal rat lung type II AE cells with a significant increase (p 0.05) in caspase-3 activity and decrease in cell proliferation at CSE concentrations of 10% and 15% (v/v). These observations indicate that cigarette smoke extract induces apoptosis by activation of caspase-3 in fetal rat lung type II AE cells in a dose-dependent manner and may potentially alter the regulated development of the lung and the appearance of the surfactant-producing type II alveolar cells which are critical for the establishment of adequate gas exchange at birth.
基金supported by the National Natural Science Foundation of China(U21A20397,22236001,42277428)the Program for HUST Academic Frontier Youth Team(2018QYTD12).
文摘This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were developed by using an unsupervised machine-learning approach.Children’s neurodevelopment,anthropometry,and respiratory outcomes in thefirst 6 years of life were assessed at different ages.In a subgroup of participants,we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs.We identified 6 FGTs:early decelerating,early decelerating with late catch-up growth,early accelerating,early accelerating with late medium growth,late decelerating,and late accelerating.The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development,mental development,intelligence quotient,and lung function and a lower risk of behaviour and respiratory problems.Compared with the optimal FGT,early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function,while early accelerating FGT was associated with more severe autistic symptoms,poor lung function,and increased risks of overweight/obesity.Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs,whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT.Thesefindings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism.The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease,but further research on related mechanisms is still needed.
文摘Background 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. Methods 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. Results 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 [I 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). Conclusions 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. Chin Med J 2009; 122(17):2013-2016
文摘To investigate whether treatment with retinoic acid (RA) could improve level of lung alveolarization and influence lung collagen in newborn rats exposed to hyperoxia, newborn Sprague-Dawley rats aged 2 days were randomly assigned to 8 groups:(1) air, (2) O 2, (3) air+NS, (4) O 2+NS, (5) air+dex, (6) O 2+dex, (7) air+RA and (8) O 2+RA. Group 2, 4 6 and 8 were kept in chambers containing 85 % oxygen, the values were checked 3 times a day. The other 4 groups were exposed to room air. Level of alveolarization and lung collagen were analyzed at age of 14 or 21 days through radial alveolar counts, alveolar airspace measurements, type Ⅰ, Ⅲ collagen immunohistochemical methods (SP method) and image processing system. Transforming growth factor-β receptors and procollagen mRNA accumulation were examined at age of 14 days through immunohistochemical methods and in situ hybridization. Our results showed that radial alveolar counts were increased and distal airspace was enlarged in group 8. TypeⅠcollagen was markedly increased, and transforming growth factor-β receptors and procollagen mRNA were decreased by retinoic acid in bronchial epithelial cells, alveolar epithelial cells and alveolar intersitium. It is concluded that retinoic acid can partially reverse lung development arrest during exposure to hyperoxia by increasing lung collagen.
基金Supported by the National Key Technology Research and Development Program of China during the 9th Five-Year Plan Period (No. 96-904-06-08)
文摘To evaluate the effects of Jinye Baidu Granule (金叶败毒颗粒, JYBDG), a traditional Chinese medicine compound prescription, on fetal growth and development with maternal active human cytomegalovirus infection. Methods: A prospective, randomized and controlled trial was adopted during January 1996 to June 2002. From the pregnant women with an abnormal pregnant history, 240 cases were screened to be infected by human cytomegalovirus (HCMV) by enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). They were assigned according to the random number table to two groups. The 122 cases in the treatment group were administrated with JYBDG, one package each time, three times a day for two continuous weeks, while the other 118 in the control group did not receive any treatment. The negative conversion rate of both HCMV-IgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate between the two groups were compared, and fetal growth and development in partial fetuses were also observed. Results: The negative conversion rate of both HCMV-IgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate in the treatment group were 77. 05% (94/122), 48.98% (48/98) and 21.74% (10/46) respectively, while those in the control group were 38. 14% (45/118), 67.50% (54/80) and 52.63% (20/38) respectively, all showing significant difference between the two groups (P〈0.01). Totally 35 normal infants and 11 abnormal infants were born in the treatment group, and the number in the control group was 20 and 18 respectively, and comparison between the two groups showed significant difference (P〈0.01). Six months of child birth, the scores of both mental development index (MDI) and psychomotor development index (PDI) of infants were higher in the treatment group (20 cases) than those in the control group (20 cases), but there was no significant difference between the two groups (P〉0.05). Conclusion: JYBDG could decrease the intrauterine transmission of HCMV and is beneficial to fetal growth and development.