ABSTRACT
With the progress of perinatal medicine, the survival rate of premature infants has been greatly improved, but the incidence of preterm related complications has also increased, including growth retardation, premature brain injury, retinopathy of prematurity, bronchopulmonary dysplasia and necrotizing enterocolitis.Insulin-like growth factor-1(IGF-1)specifically binds to IGF-1 receptor to activate intracellular signaling pathways, so that can promote cell growth, proliferation and differentiation, and inhibit apoptosis.IGF-1 is involved in the development of the heart, brain, lung, and other important organs and promotes tissue growth, so it plays an important role in fetal intrauterine development and neonatal extrauterine growth.At present, some clinical trials have found that recombinant IGF-1 and its binding protein-3 can play a role in the prevention and treatment of retinopathy of prematurity and bronchopulmonary dysplasia, bringing hope for the prevention and treatment of these refractory complications of prematurity.In this review, the function of IGF-1 and its role in preterm related complications are reviewed.
ABSTRACT
Objective@#Previous studies have found abnormal proliferation and transdifferentiation of alveolar epithelial cells(AECs)in hyperoxic lung injury of neonatal rats.The purpose of this study was to clarify the expression of zonula occludens 1(ZO-1) and ZO-1 related nucleic acid binding protein(ZONAB)in AECs in hyperoxic lung injury model, in order to investigate its effect on the proliferation and transdifferentiation of AECs in the injured lung tissue.@*Methods@#Full-term neonatal Wistar rats were randomly divided into two groups within 12 h after birth, model group(inhaled oxygen concentration 85%)and control group(inhaled air). Lung specimens were collected at 7, 14 and 21 days after exposure.The expression of ZONAB in typeⅡalveolar epithelial cells(AECⅡ)was observed by double immunofluorescence staining.At the same time, AEC Ⅱ was isolated from lung tissues of animal models at these time points, and the expression levels of ZO-1, ZONAB protein and mRNA in lung tissues and AECⅡof the two groups were detected by Western blot and Real-Time PCR.In addition, AEC Ⅱ was isolated from lung tissue of normal newborn rats and then divided into model group(85% oxygen concentration)and control group(21% oxygen concentration). After 48 hours of culture in vitro, the expression levels of ZO-1, ZONAB protein and mRNA were detected, and the expression level and location of ZONAB were observed by immunofluorescence staining.@*Results@#Double immunofluorescence staining showed that the expression of ZONAB in AECⅡin model group was significantly lower than that in control group.The protein and mRNA expression levels of ZO-1 and ZONAB in AECⅡisolated from lung tissue of model group were both significantly lower than those from control group, starting from 7 d after hyperoxia exposure.AECⅡisolated from lung tissue of normal newborn rats, were then incubated for 48 hours under hyperoxia or normoxia in vitro, the protein and mRNA expression levels of ZO-1 and ZONAB significantly decreased in model group compared with those in control group.The results of immunofluorescence staining showed that the expression of ZONAB was higher in AECⅡof the control group, and ZONAB was mostly located in the junction and nucleus of cells, while the expression of ZONAB in the model group significantly decreased than that in the control group, and the expression sites were clustered in the cytoplasm, with little expression in the junction and nucleus.@*Conclusion@#ZO-1, as a tight junction-related protein, is down-regulated in hyperoxic lung injury model.In addition to destroying pulmonary epithelial barrier to mediate pulmonary edema, it also participated in the regulation of proliferation and differentiation of AECs by regulating transcription factor ZONAB, suggesting that this may be another pathway leading to hyperoxic lung injury.
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Objective To clinically analyze the incidence of early extrapulmonary complications in premature infants with bronchopulmonary dysplasia(BPD),including periventricular intraventricular hemorrhage(PVH-IVH),white matter injury(WMI),parenteral nutrition associated cholestasis(PNAC) and metabolic bone disease(MBD),in order to direct the prevention and monitoring of these complications in BPD patients.Methods The clinical data of premature infants who were admitted to the neonatal department between September 2014 and December 2015 was retrospectively analyzed.A total of 87 premature infants diagnosed with BPD were studied as BPD group,while other 90 premature infants without BPD who were hospitalized at the same time were randomly selected as non BPD group.The occurrence of several common extrapulmonary complications was compared between two groups,including PVH-IVH,WMI,PNAC and MBD.Results The incidence of PVH-IVH in BPD group increased compared with non BPD group[(26.4%(23/87) vs 11.1%(10/90)] (P＜0.01),grade Ⅰ-Ⅱ PVH-IVH was more often seen in the BPD group too[24.1%(21/87) vs.11.1%(10/90)](P＜0.05),although the difference between two groups regarding the incidence of grade Ⅲ-Ⅳ PVH-IVH was not significant (P＞0.05).The incidence of WMI in BPD group was much higher than that in non BPD group[33.3%(29/87) vs 16.7%(15/90)] (P＜0.05),especially periventricular leukomalacia,the severe type of WMI,was more often found in BPD group than that in non BPD group[13.7%(12/87) vs 2.2%(2/90)](P＜0.05).The incidences of PNAC[22.9%(20/87) vs 5.5%(5/90)],MBD[17.2%(15/87) vs 3.3%(3/90)] and MBD with imaging changes[6.9%(6/87) vs 0] were all higher in BPD group compared with non BPD group,with significant differences between the two groups (P＜0.05).Conclusion BPD patients are more likely to have early extrapulmonary complications like PVH-IVH,WMI,PNAC and MBD than other preterm infants.It is crucial to prevent these complications reasonably and monitor them regularly for the BPD patients in order to improve the quality of life.
ABSTRACT
As a Y-box transcdption factor,ZONAB performs biological functions of promoting the proliferation and inhibiting the differentiation of epithelial cells,regulating the function of tight junctions,as well as promoting the epithelial-mesenchymal transition.ZONAB plays its transcriptional activity by interacting with other tight junction elements and genes,proteins,enzymes and transcription factors which are enrolled in the cell cycle.Meanwhile,its transcriptional activity is also regulated by many other factors.ZONAB takes part in the proliferation,differentiation of epithelial cells,stress reaction,organogenesis and oncogenesis progress,which has been proved to be associated with the genesis and development of many diseases.The regulation mechanism and clinical significance of ZONAB has been the focus at home and abroad.