Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) using microarray and to predict special target genes using bioinformatics methods in the neonatal rat hippocampus after normobaric hy...Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) using microarray and to predict special target genes using bioinformatics methods in the neonatal rat hippocampus after normobaric hyperoxia exposure, and to unravel the molecular mechanisms of developing brain injury induced by normobaric hyperoxia. Methods: Eight neonatal Sprague-Dawley rats at postnatal 1 day were divided equally between a control group and an experimental group, followed by 24-hour exposure to 21% oxygen and (95 ± 5) % oxygen, respectively. Total RNAs were extracted from the rat hippocampus. Three samples were randomly selected from each group to detect differentially expressed mRNA profiles using the affymetrix GeneChip Rat Genome 230 2.0 Array. Differentially expressed miRNA profiles were determined by miRNA enrichment analysis. The starBase software was applied to predict target genes abundantly expressed in the hippocampus, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for bioinformatics analysis. Results: Microarray analysis revealed 681 differentially expressed miRNAs in the neonatal rat hippocampus after normobaric hyperoxia exposure. Only one miRNA, miR-489-5p, was significantly upregulated (P Mdfic. The other 680 miRNAs were significantly downregulated (P P Gjb6 and Bnc2. KEGG analysis indicated that differentially expressed miRNAs were closely related to multiple signaling pathways. Conclusions: Differentially expressed miRNA profiles in the neonatal rat hippocampus after normobaric hyperoxia exposure may be involved in the physiopathological processes of developmental midbrain injury induced by normobaric hyperoxia.展开更多
Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxi- dative stress. By contr...Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxi- dative stress. By contrast, normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic/hypoxic disease. Rats inhaled normobaric oxygen （95% 02） for 6 consecutive days, and then a rat model of focal cerebral ischemia was established. Nisst and 2,3,5-triphenyltetrazolium chloride （TTC） staining revealed that normobaric oxygen pretreat- ment improved neurological deficits and reduced infarct volume. Immunohistochemical staining and western blot assay revealed that the expression of hypoxia-inducible factor-la, Notch-l, vascular endothelial growth factor and erythropoietin were increased. Behavioral studies also verified that neurological deficit scores increased. The hypoxia-inducible factor inhibitor 2-methoxyestradiol treatment at 1 hour before administration of normobaric oxygen could suppress the protective effect of normobaric oxygen. Given these observations, normobaric oxygen pretreatment may alleviate cerebral ischemic injury via the hypoxia-inducible factor signal pathway.展开更多
BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and d...BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into osteoblasts.Interestingly,osteocalcin(associated to energy metabolism)was upregulated.Vascular endothelial growth factor an expression and low-density lipoprotein receptor related protein 5/6/dickkopf Wnt signaling pathway inhibitor 1(associated to Wnt/β-catenin pathway activation)increased in osteoblasts.Yet,they decreased in adipocytes after CH treatments,mainly with the longest hypoxia times.However,the same CH treatments increased the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio in both cell types.An increase in total bone mineral density was observed in elderly people exposed to CH,but not in specific regions.The percentage of fat did not vary between groups.CONCLUSION CH may have positive effects on bone health in the elderly,due to its possible inhibitory effect on bone resorption,by increasing the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio.展开更多
To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats wer...To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.展开更多
Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD...Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.展开更多
Purpose Main purposes of pre-acclimatization by hypoxia conditioning(HC)are the prevention of high-altitude illnesses and maintenance of aerobic exercise performance.However,robust evidence for those effects or eviden...Purpose Main purposes of pre-acclimatization by hypoxia conditioning(HC)are the prevention of high-altitude illnesses and maintenance of aerobic exercise performance.However,robust evidence for those effects or evidence-based guidelines for exposure strategies,including recommendations to ensure safety,are largely lacking.Therefore,we summarize the current knowledge on the physiology of acclimatization to hypoxia and HC with the aim to derive implications for pre-acclimatization strategies before going on high-altitude treks and expeditions.Methods Based on the literature search and personal experience,core studies and important observations have been selected in order to present a balanced view on the current knowledge of high-altitude illnesses and the acclimatization process,specifically focusing on pre-acclimatization strategies by HC.Results and Conclusions It may be concluded that in certain cases even short periods(e.g.,7 h)of pre-acclimatization by HC are effective,but longer periods(e.g.,>60 h)are needed to elicit more robust effects.About 300 h of HC(intermittently applied)may be the optimal preparation for extreme altitude sojourns,although every additional hour spent in hypoxia may confer further benefits.The inclusion of hypobaric exposures(i.e.,real altitude)in pre-acclimatization protocols could further increase their efficacy.The level of simulated altitude is progressively increased or individually adjusted ideally.HC should not be terminated earlier than 1-2 weeks before altitude sojourn.Medical monitoring of the pre-acclimatization program is strongly recommended.展开更多
文摘Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) using microarray and to predict special target genes using bioinformatics methods in the neonatal rat hippocampus after normobaric hyperoxia exposure, and to unravel the molecular mechanisms of developing brain injury induced by normobaric hyperoxia. Methods: Eight neonatal Sprague-Dawley rats at postnatal 1 day were divided equally between a control group and an experimental group, followed by 24-hour exposure to 21% oxygen and (95 ± 5) % oxygen, respectively. Total RNAs were extracted from the rat hippocampus. Three samples were randomly selected from each group to detect differentially expressed mRNA profiles using the affymetrix GeneChip Rat Genome 230 2.0 Array. Differentially expressed miRNA profiles were determined by miRNA enrichment analysis. The starBase software was applied to predict target genes abundantly expressed in the hippocampus, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for bioinformatics analysis. Results: Microarray analysis revealed 681 differentially expressed miRNAs in the neonatal rat hippocampus after normobaric hyperoxia exposure. Only one miRNA, miR-489-5p, was significantly upregulated (P Mdfic. The other 680 miRNAs were significantly downregulated (P P Gjb6 and Bnc2. KEGG analysis indicated that differentially expressed miRNAs were closely related to multiple signaling pathways. Conclusions: Differentially expressed miRNA profiles in the neonatal rat hippocampus after normobaric hyperoxia exposure may be involved in the physiopathological processes of developmental midbrain injury induced by normobaric hyperoxia.
基金supported by the National Natural Science Foundation of China,No.81000523the grant from Peking University Health Science Center for the New Teacher Funding,No.BMU20090463
文摘Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxi- dative stress. By contrast, normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic/hypoxic disease. Rats inhaled normobaric oxygen （95% 02） for 6 consecutive days, and then a rat model of focal cerebral ischemia was established. Nisst and 2,3,5-triphenyltetrazolium chloride （TTC） staining revealed that normobaric oxygen pretreat- ment improved neurological deficits and reduced infarct volume. Immunohistochemical staining and western blot assay revealed that the expression of hypoxia-inducible factor-la, Notch-l, vascular endothelial growth factor and erythropoietin were increased. Behavioral studies also verified that neurological deficit scores increased. The hypoxia-inducible factor inhibitor 2-methoxyestradiol treatment at 1 hour before administration of normobaric oxygen could suppress the protective effect of normobaric oxygen. Given these observations, normobaric oxygen pretreatment may alleviate cerebral ischemic injury via the hypoxia-inducible factor signal pathway.
基金Supported by Government of Extremadura GAEDAF Research Group,No.GR18003Ministerio de Educación,Cultura y Deporte,No.FPU15/00452and Instituto de Salud Carlos III,No.PI15/01857 and No.PI18/01659.
文摘BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into osteoblasts.Interestingly,osteocalcin(associated to energy metabolism)was upregulated.Vascular endothelial growth factor an expression and low-density lipoprotein receptor related protein 5/6/dickkopf Wnt signaling pathway inhibitor 1(associated to Wnt/β-catenin pathway activation)increased in osteoblasts.Yet,they decreased in adipocytes after CH treatments,mainly with the longest hypoxia times.However,the same CH treatments increased the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio in both cell types.An increase in total bone mineral density was observed in elderly people exposed to CH,but not in specific regions.The percentage of fat did not vary between groups.CONCLUSION CH may have positive effects on bone health in the elderly,due to its possible inhibitory effect on bone resorption,by increasing the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio.
文摘To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.
文摘Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.
文摘Purpose Main purposes of pre-acclimatization by hypoxia conditioning(HC)are the prevention of high-altitude illnesses and maintenance of aerobic exercise performance.However,robust evidence for those effects or evidence-based guidelines for exposure strategies,including recommendations to ensure safety,are largely lacking.Therefore,we summarize the current knowledge on the physiology of acclimatization to hypoxia and HC with the aim to derive implications for pre-acclimatization strategies before going on high-altitude treks and expeditions.Methods Based on the literature search and personal experience,core studies and important observations have been selected in order to present a balanced view on the current knowledge of high-altitude illnesses and the acclimatization process,specifically focusing on pre-acclimatization strategies by HC.Results and Conclusions It may be concluded that in certain cases even short periods(e.g.,7 h)of pre-acclimatization by HC are effective,but longer periods(e.g.,>60 h)are needed to elicit more robust effects.About 300 h of HC(intermittently applied)may be the optimal preparation for extreme altitude sojourns,although every additional hour spent in hypoxia may confer further benefits.The inclusion of hypobaric exposures(i.e.,real altitude)in pre-acclimatization protocols could further increase their efficacy.The level of simulated altitude is progressively increased or individually adjusted ideally.HC should not be terminated earlier than 1-2 weeks before altitude sojourn.Medical monitoring of the pre-acclimatization program is strongly recommended.
