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ObjectiveTo investigate the intervention effect of Buzhong Yiqitang （BZYQT） on pulmonary inflammation in mice induced by chronic intermittent hypoxia （CIH） and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups： normoxia group， model group （exposed to CIH）， and low-， medium-， and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment， while the model group and the low-， medium-， and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups， the BZYQT （8.1， 16.2， 32.4 g·kg-1·d-1） was administered orally 30 min before placing the mice in the hypoxic chamber， while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling， pulmonary function of the mice was measured using an EMKA animal lung function analyzer， and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α） in the serum， as well as angiotensin Ⅱ （Ang Ⅱ） and angiotensin-（1-7） ［Ang（1-7）］ in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6， IL-8， TNF-α， angiotensin-converting enzyme 2 （ACE2）， and mitochondrial assembly receptor （Mas）. ResultCompared with the normoxia group， the model group showed significant abnormalities in lung function （P<0.05， P<0.01）， lung tissue changes， such as thickening of alveolar walls and inflammatory cell infiltration， increased levels of IL-6， IL-8， TNF-α in the serum and Ang Ⅱ in lung tissue （P<0.01）， decreased level of Ang（1-7） （P<0.01）， increased protein expression of IL-6， IL-8， and TNF-α， and decreased protein expression of ACE2 and Mas （P<0.05， P<0.01）. Compared with the model group， the BZYQT groups showed improvement in lung function （P<0.05， P<0.01）， and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins （P<0.05， P<0.01）， and a significant increase in ACE2 and Mas protein expression （P<0.05， P<0.01）. ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang（1-7）-Mas axis to inhibit inflammatory responses.
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OBJECTIVE@#To investigate the expression and localization of metabotropic glutamate receptors 7 and 8 (mGluR7/8) in rat superior cervical ganglion (SCG) and their changes in response to chronic intermittent hypoxia (CIH).@*METHODS@#We detected the expressions of mGluR7 and mGluR8 in the SCG of 8-week-old male SD rats using immunohistochemistry and characterized their distribution with immunofluorescence staining. The expression of mGluR7 and mGluR8 in the cytoplasm and nucleus was detected using Western blotting. A 6-week CIH rat model was established by exposure to intermittent hypoxia (6% oxygen for 30 s followed by normoxia for 4 min) for 8 h daily, and the changes in systolic blood pressure, diastolic blood pressure and mean arterial pressure were measured. The effect of CIH on expression levels of mGluR7 and mGluR8 in the SCG was analyzed using Western blotting.@*RESULTS@#Positive expressions of mGluR7 and mGluR8 were detected in rat SCG. mGluR7 was distributed in the neurons and small fluorescent (SIF) cells with positive staining in both the cytoplasm and nuclei, but not expressed in satellite glial cells (SGCs), nerve fibers or blood vessels; mGluR8 was localized in the cytoplasm of neurons and SIF cells, but not expressed in SGCs, nerve fibers, or blood vessels. Western blotting of the nuclear and cytoplasmic fractions of rat SCG further confirmed that mGluR7 was expressed in both the cytoplasm and the nucleus, while mGluR8 exists only in the cytoplasm. Exposure to CIH significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure of the rats (all P < 0.001) and augmented the protein expressions of mGluR7 and mGluR8 in the SCG (P < 0.05).@*CONCLUSION@#mGluR7 and mGluR8 are present in rat SCG but with different localization patterns. CIH increases blood pressure of rats and enhanced protein expressions of mGluR7 and mGluR8 in rat SCG.
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Male , Animals , Rats , Rats, Sprague-Dawley , Superior Cervical Ganglion , Receptors, Metabotropic Glutamate , HypoxiaABSTRACT
Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of
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Animals , Rats , Adiponectin/genetics , Hypoxia , Islets of Langerhans , Mitochondrial Dynamics , Rats, WistarABSTRACT
High altitude (HA) mining operations are a very important business in Chile, but reduced availability of oxygen affects the sleep quality, increasing the risk of accidents. An important regulator of sleep-wake cycle is the hormone Melatonin, produced by pineal gland as a sleep inductor. The aim of this study is to evaluate the effect of high altitude (4,500 m) on the quality of sleep of workers undergoing to Chronic Intermittent Hypobaric Hypoxia (CIHH) using self-reported surveys of sleepiness and sleep quality, measurement of sleep apnea (using nocturnal oximetry) and serum levels of melatonin. The Desaturation index (ID4) results revealed higher HA scores compared to sea level (SL). Regarding melatonin levels, the results show that it is increased in HA versus SL and this increase would be related to oxygen saturation during sleep. These data link sleep quality in HA to its melatonin levels, suggesting that melatonin may be a potential biomarker for sleep quality.
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Humans , Male , Altitude Sickness , Miners , Sleep Quality , Melatonin/blood , Oximetry , Chile , Oxygen Saturation , HypoxiaABSTRACT
Objective To investigate the effects of chronic intermittent hypoxia on somatotropic axis hormone levels in rats.Methods Mature male Wistar rats were exposed to air or intermittent hypoxia randomly.The serum levels of growth hormone-releasing hormone (GHRH),growth hormone (GH) and somatostatin (SS) were measured before exposure,at the 4th,8th,and 12th week after exposure.Different hormone levels in two groups were compared and analyzed.Results Compared with the control group,GHRH levels in chronic intermittent hypoxic group showed a significant decline at the 4th week [(732.77± 46.99)pg/ml vs.(893.59±40.00) pg/ml,P＜0.05],while SS levels at the 8th week [(30.71 ±2.27) pg/ml vs.(44.69±3.36) pg/ml,P＜0.05] and GH levels at the 12th week [(1.20±0.29) ng/ml vs.(2.06±0.13) ng/ml,P＜0.05]were similarly reduced.As the duration of intermittent hypoxia was prolonged,the GHRH levels did not decrease further [4th week (732.77±46.99) pg/ml vs.8th week (607.54± 131.61) pg/ml vs.12th week (730.05±40.63) pg/ml,P＞0.05].However,the serum SS levels decreased further from the 8th week to the 12th week [(30.71±2.27) pg/ml vs.(24.41±4.06) pg/ml,P＜0.05].Conclusion Chronic intermittent hypoxia might inhibit the function of somatotropic axis.Hypothalamic hormones are the earlyonesto be influenced,thereafter the entire axis.
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OBJECTIVE@#To explore the effects of hydrogen on liver injury in chronic intermittent hypoxia rats and the related oxidative stress mechanism.@*METHODS@#Twenty-four male adult SD rats were randomly divided into 3 groups(=8):the normoxia group (Norm), the chronic intermittent hypoxia group (CIH), the chronic intermittent hypoxia and hydrogen group (H + CIH). Rats in Norm group were exposed in air, those in the other 2 groups suffered from chronic intermittent hypoxia conditions for 5 weeks. Before the CIH treatment, rats in H+CIH group inhaled hydrogen gas at 67% concentration for 1 hour. The serum biochemical indicators of oxidative stress, pro-inflammatory cytokine, liver enzyme and blood lipid were inspected after five weeks treatment, the pathological changes of liver tissue were also observed in the transmission electron microscope.@*RESULTS@#Compared with Norm group, the microstructure of liver cells was severely injured, and the serum levels of glutamic-pyruvic transaminase(ALT),glutamic-oxalacetic transaminase (AST) were significantly higher in CIH group (<0.05); the serum level of 8-hydroxy-2 deoxyguanosine(8-OHdG) and interleukin-6(IL-6) was significantly higher, the serum level of superoxide dismutase (SOD) was significantly lower. Compared with CIH group, the pathology of liver microstructure were significantly improved and the serum levels of ALT, AST were significantly lower in H+CIH group (<0.05); the serum levels of 8-OHdG and IL-6 were significantly lower, the serum level of SOD was significantly higher. Compared with Norm group, the serum level of IL-1 was higher, the serum level of TC, TG, and low density lipoprotein(LDL) were lower, but there was no statistical difference with those in CIH group. There was no statistical difference in the serum level of high density lipoprotein (HDL)among the three groups.@*CONCLUSIONS@#Pre-treatment with hydrogen could improve the liver injury caused by chronic intermittent hypoxia, and reducing oxidative stress level for protecting the liver cells damage.
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Animals , Male , Rats , Hydrogen , Pharmacology , Hypoxia , Liver , Liver Diseases , Therapeutics , Oxidative Stress , Random Allocation , Rats, Sprague-DawleyABSTRACT
Objective To investigate the effect of chronic intermittent hypoxia(CIH)on the cardiovascular system in anesthetized rats. Methods A totally of 72 male SD rats were randomly divided into three groups(n=24),namely the ormoxia control group(control group), the normoxia anesthesia group(model group)and the chronic intermittent hypoxia group(CIH group).Rats of the control group breathe nor-mally.The model group was given intraperitoneal injection of 10%hydration with 0.3 mL/kg,and the CIH group was given chronic intermit-tent hypoxic stimulation with 8 h/d in addtion to the model group.The difference of ultrasonic echocardiography data,blood pressure,endothe-lin type-1,and endothelial nitric oxide synthase(eNOS)in rats of the three groups were compared.After 28 days,these rats were sacrificed to observe the changes of myocardial cell structure.Results In the control group,the myocardial morphology was normal,the cells arranged e-venly,and there was no swelling and inflammation.In the model group,the myocardial cells were evenly arranged without hypertrophy and in-flammatory changes.In the CIH group,the myocardial cells in the hypoxic group were not evenly arranged,and hypertrophy,swelling,deform-ation,hyperchromia,and obvious inflammatory changes of the myocardial tissue were observed.In the control group,myocardial cell nucleus and cytoplasm were uniformly arranged,and there was no obvious changes in the model group.On the contrary,myocardial cell morphology changed obviously in the CIH group,with the cell morphology and size of the inhomogeneity increased, and the color of the apoptosis cells changes from light to dark.The tail artery systolic pressure of rats in CIH group was significantly higher than that of the control group and the model group,and the LVEF of CIH group was significantly lower than that of the other two groups(P<0.05).Ultrasound detection value sug-gests that the LVID and left ventricular of rats in the CIH group were slightly larger,and the diastolic function was normal.The LVDs of the model group and the CIH group were both higher than that of the control group with statistically significant difference(P<0.05).The RBC, HCT,dp/dtmax,and -dp/dtmax in the CIH group were significantly higher than those of the control group and the model group(P<0.05). Serum levels of endothelin-1 in CIH group were significantly higher than that of control group and model group,while the summation of serum NO2-/NO3-and eNOS in CIH group were significantly lower than those of the control group and the model group(P<0.05).Conclusion Chronic intermittent hypoxia can cause cardiac dysfunction in anesthetized rats,which may lead to the imbalance of serum endothelin-1 and NO levels,leading to endothelial dysfunction and myocardial injury.
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Objective To investigate the effects of chronic intermittent hypoxia on the adipose factor and the expressions of insulin receptor substrate 2 (IRS-2),glucose transporter 2 (GLUT-2) and leptin in rat liver.Methods Twenty-four mature SD rats were randomly divided into 3 groups:control group (UC),chronic intermittent hypoxia group (CIH) and reoxygenation group (RH).The arterial blood gas analysis was performed after the establishment of rat model.The serum fasting blood glucose (FBG) and fasting insulin (FINS) in each group were detected by peroxidase method;the concentrations of free fatty acids (FFA) and leptin were detected by ELISA.The expressions ofmRNA and protein of GLUT-2,IRS-2 and leptin were detected by qRT-PCR and Western blotting.Results The serous concentrations of FBG,FINS,FFA and leptin were significantly higher in CIH group than in UC group (P＜0.05),and were dramatically higher in RH group than in both CIH group (P=0.003) and UC group (P=0.000).Western blotting and qRT-PCR detection showed that the protein and mRNA expressions of GLUT-2 and IRS-2 were significantly lower in CIH group than in RH group of rat liver (P＜0.05),while were markedly lower in RH group than in UC group (P＜0.05);the expressions of leptin protein and mRNA were significantly higher in CIH group than in RH group (P＜0.05),while were obviously higher in RH group than in UC group of rat liver (P＜0.05).Conclusion Insulin resistance induced by chronic intermittent hypoxia may be associated with the elevation of serum FFA and leptin,and be related to the decreased expression of GLUT-2 and IRS-2 and increased expression of leptin in liver.
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Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH).However,little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy,and whether specific hypertrophyrelated microRNAs are involved in the modulation.MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia.This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy.H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days.The size of cardiomyocytes,and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR,respectively.MiR-31 mimic or Ro 31-8220,a specific inhibitor of protein kinase C epsilon (PKCε),was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes.PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting.The results showed that CIH induced obvious enlargement of cardiomyocytes,which was paralleled with increased atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels.All these changes were reversed by the treatment with atorvastatin.Meanwhile,miR-31 was increased by CIH in vitro.Of note,the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31.Moreover,overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes.Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε.These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.
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Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH).However,little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy,and whether specific hypertrophyrelated microRNAs are involved in the modulation.MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia.This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy.H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days.The size of cardiomyocytes,and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR,respectively.MiR-31 mimic or Ro 31-8220,a specific inhibitor of protein kinase C epsilon (PKCε),was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes.PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting.The results showed that CIH induced obvious enlargement of cardiomyocytes,which was paralleled with increased atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels.All these changes were reversed by the treatment with atorvastatin.Meanwhile,miR-31 was increased by CIH in vitro.Of note,the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31.Moreover,overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes.Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε.These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.
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Objective:To study the change of Porphyromonas gingivalis (P.gingivalis) in rat gingival crivicular tluid (GCF) under chronic intermittent hypoxia.Methods:32 male SD rats were randomly divided into 4 groups (n =8):normoxia control group (A),normoxia with periodontitis group (B),intermittent hypoxia group(C),and intermittent hypoxia with periodontitis (D).Periodontitis model was established by orthodontic silk ligation at the maxillary second molar neck and high sugar diet.The rats in normoxia and hypoxia group were raised respectively under the condition of ordinary oxygen and chronic intermittent hypoxia respectively.After 8 weeks,GCF of the target teeth was collected,P.gingivalis was quantified by real-time fluorescent quantitative PCR.Results:P.gingivalis was detected in all groups.P.gingivalis in group D was more than in other groups(P ＜0.05);meanwhile,P.gingivalis in group B was more than in group A(P ＜0.05).Conclusion:Chronic intermittent hypoxia can aggravate the severity of periodontitis,which is associated with the increase of P.gingivalis in GCF.
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Objective To investigate the effects of chronic intermittent hypoxia and on GLUT-2, IRS-2 expression in the rat kidney .Methods Rats were randomly divided into control group ( control) , chronic intermittent hypoxia group (CIH), chronic intermittent hypoxia reoxygenation group (RH).The chronic intermittent hypoxia animal models were developed , arterial blood gas analysis was immediately carried out .Serum glucose was measured by peroxidase and serum insulin was detected by radioimmunoassay .After Removing the kidney tissue of rats ,protein expression of GLUT-2, IRS-2 were detected with Western blot and immunohistochemical , mRNA expression of GLUT-2,IRS-2 were observed by qPCR .Results Oximetry in the control group was ≥95%, oxygen saturation in the CIH group was ≤85%, oxygen saturation in the RH group was ≥86%; fasting blood glucose , serum insulin and insulin resistance index in the CIH group were significantly higher those of control group and RH group ( P<0.05);RH group was higher than control group (P<0.05).Protein and mRNA expression of GLUT-2, IRS-2 in the CIH group were higher than the control group and RH group ( P<0.05 ); RH group was higher than control group (P<0.05).Conclusions Chronic intermittent hypoxia can increase blood glucose ,upregulate the expres-sion of GLUT-2 , IRS2 in the rat kidney and enhance insulin resistance and decrease insulin sensitivity .
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Yi-Qi-Fu-Mai (YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation (EYQFM), the EYQFM (1.4, 2.8, and 5.5 g·kg(-1)·d(-1)) was assessed for its heart-protective effect in a chronic intermittent hypoxia (CIH) animal model (oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc (0.151 6 g·kg(-1)·d(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions (EF), stroke volume (SV), expression of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.
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Animals , Humans , Male , Mice , Creatine Kinase , Metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Heart , Heart Injuries , Metabolism , Hypoxia , L-Lactate Dehydrogenase , Metabolism , Malondialdehyde , Metabolism , Superoxide Dismutase , MetabolismABSTRACT
Chronic intermittent hypoxia ( CIH ) caused by ob-structive sleep apnea hypopnea syndrome( OSAHS) is an impor-tant factor causing or aggravating many kinds of cardiovascular and cerebrovascular diseases. Establishing a rational animal model for intermittent hypoxia is an essential method to study the CIH related cardiovascular diseases. Recently, researchers have tended to simulate intermittent hypoxia condition by controlling the oxygen concentration of the environmental air around the ani-mals. In the paper, we summarize and compare the methods of making intermittent hypoxia animal model in recent literature, from aspects of experimental animals, gas control apparatus, gas species and concentration, intermittent hypoxia treatment time, and anoxic cycle mode.
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[ ABSTRACT] AIM: To investigate the effect of chronic intermittent hypoxia on AMP-activated protein kinase ( AMPK) pathway in the brain of young rats.METHODS:Part one:SD mice (3~4 weeks old) were randomly divided into 4 groups (n=8): simulated air control group for 2 weeks (2AC), chronic intermittent hypoxia group for 2 weeks (2IH), simulated air control group for 4 weeks (4AC) and chronic intermittent hypoxia group for 4 weeks (4IH).Part two:SD mice (3~4 weeks old) were randomly divided into 2 groups (n=8): chronic intermittent hypoxia group for 4 weeks (4IH) and chronic intermittent hypoxia group treated with AMPK inhibitor for 4 weeks (4IHI).After modeling, the eight-arm maze test was performed.TUNEL method was used to detect the neuronal apoptosis in the hippocampal and pre-frontal cortical tissues.The mRNA expression of adenosine A2a receptor was examined by RT-qPCR, and the protein levels of phosphorylated AMPK (p-AMPK) and mammalian target of rapamycin (p-mTOR) were determined by Western blot. RESULTS:Compared with control group, the numbers of reference memory error ( RME) , working memory error ( WME) and total error (TE) in 2IH group and 4IH group significantly increased (P<0.01).Compared with 2IH group, the num-bers of errors in 4IH group also increased significantly (P<0.01).Compared with 4IH group, the values in 4IHI group significantly decreased.Compared with control group, the neuronal apoptosis of hippocampus and prefrontal cortex in 2IH group and 4IH group increased, and that in 4IH group was more evident (P<0.05).In 4IHI group, the neuronal apopto-sis decreased.The mRNA expression of adenosine A2a receptor in the hippocampal and cortical tissues in 2IH group and 4IH group was higher than that in control group.The protein level of p-AMPK was higher, and p-mTOR was lower in 2IH group and 4IH group, and those in 4IH group were more evident (P<0.05).Compared with 4IH group, the protein level of p-AMPK was lower, and p-mTOR was higher in 4IHI group.CONCLUSION: Chronic intermittent hypoxia induces neuronal apoptosis, resulting in impairment of learning and memory in a time-dependent manner by upregulating adenosine A2a receptor, activating AMPK activity, and inhibiting mTOR phosphorylation in rats.
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Objective To explore the role of Foxp3+ T cells (Tregs) in liver injury induced by chronic intermittent hypoxia. Methods Thirty-two male Wister rats were divided into four groups:control group (A), high-fat diet group (B), intermittent hypoxia group (C), and high-fat diet and intermittent hypoxia group (D). After 4 weeks, blood samples were collected and livers were surgically removed. Using the standard automatic clinical analyzer to test serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL- C), alanina aminotransferase (ALT) and aspartato aminotransferase (AST). The MDA content of liver tissue was measured by colorimetrc method. The levels of TNF-αand IL-1βwere measured by radiommunoassay, and the expression of Foxp3 protein was measured by Western blotting technique. Results Serum levels of TC and LDL-C were significantly higher in B group than those of A, C and D groups, and which were higher in D group than those of A and C groups (P<0.05). There were no significant differences in serum levels of TC and LDL-C between A group and C group. Serum levels of ALT, AST, MDA, TNF-αand IL-1βwere significantly higher in C group than those of A group, and which were significantly higher in D group than those of A, B and C groups (P<0.05). There were no significant differences in these indicators between A group and B group, and between B group and C group. Foxp3 protein expression in liver was significantly lower in D group than that of other groups (P<0.05). Conclusion Foxp3+T regulatory cells involve in the regulation of hepatic injury induced by chronic intermittent hypoxia on the basis of a high-fat diet, and which may play an important role in this process of protective immune response.
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OBJECTIVE@#To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia.@*METHODS@#A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in each group. The molecular biological techniques of immunohistochemistry, RT-PCR and Western blotting were employed to detect the effect of different hypoxia time (0, 6, 12, 24 and 48 h) and different concentrations of hypoxia (0.000, 0.001, 0.010, 0.060 and 0.100 ppm) on the expression of RUNX2 and MDM21 in rats of four groups.@*RESULTS@#The expression of RUNX2 and MDM21 in each group was significantly higher than the one at other concentrations when the concentration was 0.010 ppm, with the statistical difference (P normoxic periodontitis group > hypoxia control group > hypoxia periodontitis group under the action with the concentration of 0.010 ppm for 12 h, but there was no significant difference for the comparison among groups (P > 0.05).@*CONCLUSIONS@#The condition of chronic intermittent hypoxia can reduce the expression of RUNX2 and MDM21 in rats with periodontitis and aggravate the damage of periodontal bone.
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Objective To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia. Methods A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in each group. The molecular biological techniques of immunohistochemistry, RT-PCR and Western blotting were employed to detect the effect of different hypoxia time (0, 6, 12, 24 and 48 h) and different concentrations of hypoxia (0.000, 0.001, 0.010, 0.060 and 0.100 ppm) on the expression of RUNX2 and MDM21 in rats of four groups. Results The expression of RUNX2 and MDM21 in each group was significantly higher than the one at other concentrations when the concentration was 0.010 ppm, with the statistical difference (P normoxic periodontitis group > hypoxia control group > hypoxia periodontitis group under the action with the concentration of 0.010 ppm for 12 h, but there was no significant difference for the comparison among groups (P > 0.05). Conclusions The condition of chronic intermittent hypoxia can reduce the expression of RUNX2 and MDM21 in rats with periodontitis and aggravate the damage of periodontal bone.
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Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4) and Nox subunits (p22phox, and p47phox) was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01). Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1–7) treatment. In summary, treatment with Ang-(1-7) reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.
Subject(s)
Animals , Male , Angiotensin I/pharmacology , Hypoxia/complications , Inflammation/drug therapy , Lung Injury/drug therapy , Lung Injury/etiology , Oxidative Stress/drug effects , Peptide Fragments/pharmacology , Vasodilator Agents/pharmacology , Blotting, Western , Cytokines/analysis , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Inflammation/pathology , Lung Injury/metabolism , Lung/drug effects , Lung/pathology , Malondialdehyde/analysis , Protective Agents/pharmacology , Random Allocation , Rats, Sprague-Dawley , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Sleep Apnea, Obstructive/complicationsABSTRACT
Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.