Most of perinatological phenomenona and diseases are closely related with immune reaction. Most of initial immune responses occur through innate immunity and most causes, such as mechanical damage, hypoxia, and hyperoxia, are self and microorganisms are non-self, all of which are related with immune reaction concept. However, researches on perinatology are mainly focused on specific one or two causes of perinatal diseases, so often there is limitation to understand the basic concepts and phenomenona of the perinatal diseases. Through understanding of immune reaction concept, we can apply immune reaction theory to researches in perinatology and we can understand phenomenona in perinatology through knowledge of immune reaction. Therefore it is essential to understand historical development of immunology and concept of immune reaction for researches and treatment of perinatology.
Allergy and Immunology ; Anoxia ; Hyperoxia ; Immunity, Innate ; Perinatology*

Animals ; Cecum/microbiology* ; Hyperoxia/blood* ; Microbiota ; Rats

The pathologic hallmark of new bronchopulmonary dysplasia (BPD) is an arrest in alveolarization and vascular development. Alveoli are the fully mature gas-exchange units and alveolarization denotes the process through which the developing lung attains its fully mature structure. In human, alveolarization is mainly a postnatal event and begins in utero around 35 postmenstrual weeks and continues to 2 postnatal years. Beginning of respiration with very immature lungs as a result of preterm delivery renders the immature lung to be exposed to various injuries such as mechanical stretch, hyperoxia, infection/inflammation and leads to a disruption of normal alveolarization process, which is a main pathologic finding of BPD. Better understanding of the control mechanisms of normal alveolarization process should help us to figure out the pathophysiology of BPD and discover effective preventive or therapeutic measures for BPD. In this review, the pathologic evolution of BPD from 'old' to 'new' BPD, the detailed mechanisms of normal alveolarization, and the factors that disrupt normal alveolarization will be discussed.
Bronchopulmonary Dysplasia ; Humans ; Hyperoxia ; Infant, Newborn ; Lung ; Respiration

No abstract available.
Animals ; Extracellular Matrix* ; Hyaluronic Acid* ; Hyperoxia* ; Lung Injury* ; Lung* ; Rats*

PURPOSE: To investigate the effect of curcumin, known to inhibit hypoxia-inducible factor-1, on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). METHODS: OIR was induced by exposing C57BL/6 mice on postnatal day 7 (P7) to 75% hyperoxia for 5 days, followed by 5 days in a room with normal oxygen level. Curcumin was administered intraperitoneally once a day for 5 days from P12 or intravitreally once on P13. Mice retinas on P17 were analyzed for retinal neovascularization, which was compared between curcumin-treated and control mice. RESULTS: After intraperitoneal and intravitreal administration of curcumin, qualitative assessment of retinal neovascularization of flat-mounted retina showed no significant difference compared to control retinas. Quantitative assessment of retinal neovascularization also showed no significant difference between curcumin-treated and control mice. CONCLUSIONS: Both intraperitoneal and intravitreal administration of curcumin did not reduce retinal neovascularization in an OIR mouse model. Further investigation including development of new formulations is required for the use of curcumin as an anti-angiogenic agent for retinal neovascularization.
Animals ; Curcumin* ; Hyperoxia ; Mice* ; Oxygen ; Retina ; Retinal Neovascularization ; Retinopathy of Prematurity

OBJECTIVE: To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. METHODS: Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. RESULTS: Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). CONCLUSIONS Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.
Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; Hyperoxia ; Lung ; MicroRNAs ; Rats ; Triterpenes

OBJECTIVE: To investigate the protective effect of vitamin D (VD) against hyperoxia-induced bronchopulmonary dysplasia (BPD) in newborn mice and explore the mechanism. METHODS: Thirty-six newborn mice were randomly divided into air + VD group, air + saline group, hyperoxia + VD group, and hyperoxia + saline group. In all the groups, saline or VD was administered on a daily basis intramuscular injection. After 3 weeks of treatment, the mice were weighed and cardiac blood was collected for measurement of serum VD level using ELISA, and histological examination of the lungs was performed. Radial alveolar counting (RAC) and alveolar secondary interval volume density were measured using image analysis software. The expression levels of vascular endothelial cell growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in the lung tissues were detected using Western blotting. RESULTS: The weight gain rate of the mice and the weight of the lungs were significantly higher in air + saline group and air + VD group than in the hyperoxia + saline group. The RAC was significantly lower in hyperoxic+saline group than that in hyperoxia+VD group ( < 0.001), and was significantly higher in hyperoxic+VD (125 times) than in hyperoxia + VD (1250 times) group ( < 0.01). The alveolar secondary protrusion count was significantly higher in hyperoxic+VD (1250 times) group than in hyperoxic+saline group ( < 0.001), and was significantly higher in hyperoxia+VD (125 times) group than in hyperoxia + VD (1250 times) group ( < 0.01). Compared with that in air + saline group, VEGFR2 expression was significantly lowered in hyperoxia+saline group ( < 0.05) and in air+VD group ( < 0.05); VEGFR2 expression was significantly higher in hyperoxia+VD (1250 times) group than in hyperoxia+saline group ( < 0.001) and hyperoxia+VD (125 times) group ( < 0.001); VEGFR2 expression was significantly higher in hyperoxia+VD (125 times) group than in hyperoxia+ saline group ( < 0.05). CONCLUSIONS In newborn mice with BPD, VD supplement can increase the weight of the lungs and promote lung maturation, and a higher concentration of VD can better protect the lungs and promote the growth of pulmonary blood vessels.
Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; Hyperoxia ; Lung ; Mice ; Vitamin D

In vivo ethane production in rats was used as an index of oxygen toxicity. The rats were allocated to four exposure conditions; hyperbaric oxygenation (HBO=5 ATA, 100% O2), normobaric oxygenation (NBO=1 ATA, 100% O2), hyperbaric aeration (HBA=5 ATA, 21% O2) and normobaric aeration (NBA=1 ATA, 21% O2). After 120 minutes of exposure, the rats exposed to high concentration and/or high pressure oxygen exhaled significantly larger amounts of ethane than those exposed to NBA, and the differences in ethane production between any two groups were statistically significant (p<0.01). This finding supports the hypothesis that hypothesis that hyperoxia increase oxygen free-radicals and the radicals produce ethane as a result of lipid peroxidation. It is notable that the ethane exhalation level of the HBA group was significantly higher than that of the NBO group. This difference could not be accounted for by the alveolar oxygen partial pressure difference between the two groups.
Animals ; Ethane* ; Exhalation* ; Hyperbaric Oxygenation ; Hyperoxia* ; Lipid Peroxidation* ; Oxygen ; Partial Pressure ; Rats

BACKGROUND: Exposure to hyperoxia causes extensive injury to lung tissue, which resembles the pathologic changes of the adult respiratory distress syndrome. To observe the relationship between the pulmonary oxygen toxicity and duration of exposure to oxygen, 100% oxygen was exposed to Wistar rats. METHODS: 35 rats were partitioned into 5 groups (n=7 in each group). Gr. I breathed room air. Gr. II, III, IV and V were exposed to 99~100% oxygen for 24 hrs, 48 hrs, 60 hrs and 72 hrs. Wet lung/body weight (WW/BW), dry lung/body weight (DW/BW), wet/dry lung weight (WW/DW) and I-albumin flux ratio were measured in each group. RESULTS: After exposure for 72 hrs in Gr. V, 3 rats were dead. WW/BW in Gr. I was 0.69+/-0.04 and increased to 1.10+/-0.28 in Gr.II (P<0.05), which was maintaind until 60 hrs. It showed marked increase in Gr. V; 2.16+/-0.60. DW/BW, WW/DW and I-albumin flux ratio increased after 48 hrs of hyperoxia. WW/BW and DW/BW in Gr. V and I-flux ratio in Gr. IV showed significant increase compared with Gr. I, II and III. CONCLUSIONS: The results suggest that pulmonary capillary permeability begins to change after 24 hrs of hyperoxia and that definite permeability change to albumin and fluid accumulation in the lung are demonstrable from 48 hrs-exposure to 99~100% oxygen and aggravated by duration of oxygen exposure.
Animals ; Capillaries* ; Capillary Permeability* ; Hyperoxia ; Lung ; Oxygen* ; Permeability ; Rats* ; Rats, Wistar ; Respiratory Distress Syndrome, Adult

Animals ; Bronchopulmonary Dysplasia ; etiology ; Fibroblasts ; physiology ; Humans ; Hyperoxia ; pathology ; Infant, Newborn ; Lung ; embryology ; pathology