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Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.
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Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.
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Abstract Objective The purpose of this study is to develop an animal model of Chronic Intermittent Hypoxia (CIH) and investigate the role of the TRPC5 channel in cardiac damage in OSAHS rats. Methods Twelve male Sprague Dawley rats were randomly divided into the CIH group and the Normoxic Control (NC) group. Changes in structure, function, and pathology of heart tissue were observed through echocardiography, transmission electron microscopy, HE-staining, and TUNEL staining. Results The Interventricular Septum thickness at diastole (IVSd) and End-Diastolic Volume (EDV) of rats in the CIH group significantly increased, whereas the LV ejection fraction and LV fraction shortening significantly decreased. TEM showed that the myofilaments in the CIH group were loosely arranged, the sarcomere length varied, the cell matrix dissolved, the mitochondrial cristae were partly flocculent, the mitochondrial outer membrane dissolved and disappeared, and some mitochondria were swollen and vacuolated. The histopathological examination showed that the cardiomyocytes in the CIH group were swollen with granular degeneration, some of the myocardial fibers were broken and disorganized, and most of the nuclei were vacuolar and hypochromic. Conclusion CIH promoted oxidative stress, the influx of Ca2+, and the activation of the CaN/NFATc signaling pathway, which led to pathological changes in the morphology and ultrastructure of cardiomyocytes, the increase of myocardial apoptosis, and the decrease of myocardial contractility. These changes may be associated with the upregulation of TRPC5.
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Cognitive disorders, including dementia and Alzheimer's disease, pose substantial global health challenges, demanding effective prevention and treatment strategies. Intermittent Hypoxia Therapy (IHT), involving brief exposures to reduced oxygen levels, is a novel approach with potential cognitive benefits. This study investigates the effects of Intermittent Hypoxia Therapy (IHT) on cognitive behavior in Wistar albino rats through comprehensive behavioral experiments, including the Open Field Test (OFT) and Morris Water Maze (MWM). The results reveal that IHT promotes locomotor activity, reduces anxiety-related behaviors, and positively impacts cognitive flexibility. In the OFT, the IH group exhibited increased grid crossings and distance traveled, indicating heightened locomotion, which may be associated with cognitive improvement. Furthermore, IH significantly reduced thigmotaxis behavior and the number of fecal boli, indicating reduced anxiety levels compared to the control group. While IHT did not significantly enhance spatial memory acquisition in the MWM, it improved platform recognition during the probe test. The IH group spent more time in the target quadrant, suggesting enhanced memory retrieval and recognition. Additionally, in the reverse MWM, IH demonstrated moderate improvements in cognitive flexibility, with faster latency on trial 1. These findings suggest that IHT holds promise as a non-invasive intervention for cognitive enhancement, particularly in terms of locomotor activity, anxiety reduction, and certain aspects of memory and cognitive flexibility. Further research is warranted to elucidate the underlying mechanisms and explore the potential therapeutic applications of IHT in cognitive disorders. In summary, this study highlights the cognitive benefits of IHT in rats, paving the way for future investigations and potential clinical applications in the realm of cognitive disorders.
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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
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 explore any effect of intermittent hypoxia (IH) on myocardial energy metabolism and its mechanism.Methods:Twenty-one male Sprague-Dawley rats were randomly divided into a sham operation group, a myocardial infarction group and an observation group. The latter two groups received occlusion of the left anterior descending coronary artery. The observation group then lived in an hypoxic environment intermittently for 4 hours/day, 5 days/week for four weeks, while the other 2 groups were exposed to a normal level of oxygen. The ejection fraction of the left ventricle (LVEF) was measured at 1 week after the modeling and 4 weeks after the start of the intervention. Also at that point myocardial fibrosis, mitochondrial structure, ATP content, and the protein expressions of adenosine monophosphate-activated protein kinase alpha1 (AMPKα1) and sirtuins protein family member 3 (SIRT3) were assessed in all three groups.Results:A significant decrease in the LVEF, the number of mitochondria, ATP content, AMPKα1 and SIRT3 protein were observed in the infarction group compared with the sham group. There was also a significant increase in the myocardial fibrosis index. Moreover, the LVEF decreased significantly and the myocardial fibrosis index had increased significantly in the observation group compared with the sham operation group, though the two groups exhibited no significant differences the number of mitochondria, ATP content, or the expression of AMPKα1 or SIRT3. Compared with the myocardial infarction group, in the observation group there was a significant increase in the LVEF, the number of mitochondria, ATP content, and the expression of AMPKα1 and SIRT3 protein, with a significant decrease in the fibrosis index. AMPKα1 and SIRT3 level were positively inter-correlated and positively correlated with LVEF and ATP content.Conclusions:IH intervention can promote ATP synthesis and improve mitochondrial structure by regulating the AMPKα1/SIRT3 pathway, reducing myocardial fibrosis and enhancing cardiac function.
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AIM: To study the protective effect of edaravone on renal injury induced by chronic intermittent hypoxia and its effect on Caspase-1 mediated pyroptosis signaling pathway in rats. METHODS: Twenty four SPF male SD rats were randomly divided into normal control group, intermittent hypoxia group, intermittent hypoxia + normal saline group and intermittent hypoxia + edaravone group, with 6 rats in each group. The four groups of rats were placed in the closed feeding chamber for modeling. The oxygen concentration in the NC group was maintained at about 21%; the IH group, IH + NS group and IH + EDA group were given regular input of pure oxygen, pure nitrogen and compressed air to form anoxic-reoxygenation cycle (60 s hypoxic period + 60 s reoxygenation period). During the hypoxic period, the oxygen concentration in the chamber was reduced to 6%-7%, and the rats in the IH + EDA group were intraperitoneally injected with edaravone at a dose of 5 mg/kg per day before modeling, while the rats in the IH + NS group were intraperitoneally injected with normal saline at the same dose per day. After 8 weeks of modeling, blood and kidney tissue samples were collected to measure the levels of Crea and Urea in each group. The pathological changes and fibrosis degree of kidney were observed under light microscope after HE and Masson staining. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined by chemical method. The expression levels of NLRP3, Caspase-1 and IL-1β in renal tissues were determined by immunohistochemical staining. The expression levels of caspase-1 and IL-1β in renal tissues were determined by Western blot. GSDMD and IL-18 mRNA were detected by RT-PCR. RESULTS: After intermittent hypoxia exposure, serum Crea and Urea were increased significantly (P < 0.01), renal tubules were damaged by pathology, collagen fiber deposition occurred in balloon space of renal units, MDA content was increased and SOD activity was decreased (P < 0.01). Caspase-1, NLRP3, IL-1β protein expression increased (P < 0.01 or P < 0.05), GSDMD mRNA and IL-18 mRNA amplification increased (P < 0.01); After Edaravone intervention, the above indexes showed a reverse trend compared with that after intermittent hypoxia exposure, and the pathological damage of kidney was reduced (P < 0.01 or P < 0.05). CONCLUSION: Chronic intermittent hypoxia may mediate kidney injury through oxidative stress activation of caspase-1 involved in the cell pyroptosis signaling pathway, while edaravone may inhibit the activation of pyroptosis signaling pathway by scavenging oxygen free radicals and down-regulating the level of oxidative stress in the body, thus playing a protective role in kidney.
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Intermittent hypoxia (IH) is an important pathophysiological feature of obstructive sleep apnea (OSA), but its molecular mechanism is still unclear. We aim to investigate the role of endogenous competing endogenous RNA (ceRNA) regulatory network in the development of IH in OSA rats. An intermittent hypoxic rat model of OSA was constructed by hypoxic and reoxygenation cycles. CircRNAs and mRNAs were detected in rat bronchial tissues, and 230 up-regulated and 181 down-regulated circRNAs and 1238 up-regulated and 608 down-regulated mRNAs were analyzed and screened. The results of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential circRNAs and mRNAs suggested that they were mainly associated with metabolic pathways and PI3K-Akt signaling pathways. The key circRNAs (the top six circRNAs with the largest differences) were further validated by quantitative real-time polymerase chain reaction (qRT-PCR), chr9:52042693| 52047844 and chr4: 64889575|64899587 were expressed in bronchial tissues consistent with the sequencing results, which were used to further construct the ceRNA regulatory network. Four potential ceRNA regulatory networks were identified by TargetScan and miRanda database, combined with the results of differential circRNA and mRNA. The expression of molecules in the four potential ceRNA regulatory networks was detected by qRT-PCR in bronchial and lung tissues, and the results suggested that the expression of this regulatory network, chr9:52042693|52047844-miR-351-5p-Pten, was consistent with the sequencing results. The findings indicate that chr9:52042693 | 52047844-miR-351-5p-Pten may be involved in the development and progression of obstructive sleep apnea syndrome through a ceRNA mechanism.
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Objective To explore the effect of chronic intermittent hypoxia(CIH)combined with high-fat diet(HFD)on gastroc-nemius muscle in mice and its possible mechanism.Methods A mouse model of obstructive sleep apnea hypopnea syndrome(OSAHS)combined with obesity was established by simulating CIH and HFD.Mice were divided into normal control group(NC),CIH group,HFD group,and CIH+HFD group.Hematoxylin-eosin(HE)staining was used to observe the structural changes of the gastrocnemius in each group of mice,and adenosine triphosphate(ATP)enzyme staining was used to analyze the changes in the types of muscle fibers in the gastrocnemius.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression level of MHC i-sotype genes(MHC1,MHC2),mitochondrial function related genes(Cs,Ant,NQO1,Hmox1,OGG1)gastrocnemius cells of mice;Western blot was used to detect the expression level of apoptosis-related proteins(cleaved-caspase-3),mitochondrial fusion proteins(Mfn1,Mfn2,OPA1)and mitochondrial division proteins(Drp1 Ser616,Fis1)in gastrocnemius cells of mice.Results Compared with the NC group,the gastrocnemius structure of the mice in the CIH+HFD group was significantly damaged.while the type Ⅰ muscle fibers in the gastrocnemius were decreased,the type Ⅱ muscle fibers in the gastrocnemius were increased.The expression level of MHC1mRNA in the gastrocnemius cells was decreased,and the expression level of MHC2mRNA was increased.In addition,the protein expressions of cleaved-caspase-3,mitochondrial division proteins(Drp1 Ser616 and Fis1)were significantly up-regulated in the CIH+HFD group.The mRNA or protein expressions of Cs,Ant,NQO1,Hmox1,OGG1,Mfn1 were down-regulated.Conclusion CIH combined with HFD can lead to structural and functional damage of gastrocnemius in mice,which may be related to mitochondrial dysfunction caused by mitochondrial dynamics disorder.
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Objective @#To investigate the effects and mechanism of small ubiquitin-like modifier ( SUMO) specific proteinase-1 (SENP-1) on chronic intermittent hypoxia ( CIH) induced myocardial injury in rats．@*Methods @# 32 male SD rats were randomly divided into : control group，CIH group，negative control adeno-associated virus interven- tion group (AAV-shNC) and SENP-1 shRNA adeno-associated virus intervention group (AAV-shSENP-1) ，with 8 rats in each group．After 6 weeks of CIH induction，echocardiography was performed．The levels of cardiac troponin I (cTNI) ，creatine kinase MB isoenzyme ( CKMB) ，myoglobin (Mb) ，lactate dehydrogenase (LDH) in serum and malondialdehyde (MDA) ，uperoxide dismutases ( SOD) ，glutathione ( GSH) ，interleukin( IL) -1 β , IL-6 and tumor necrosis factor-α(TNF-α) in myocardial tissue were detected by ELISA．The pathological changes of myocardial tis- sue was observed by HE staining．The reactive oxygen species ( ROS) level in myocardial tissue was detected by DCFH-DA fluorescence probe labeling．The small ubiquitin-like modifier (SUMO) level of hypoxia inducible factor- 1 α (HIF-1 α) protein in myocardial tissue was detected by kit．The mRNA and protein levels of SENP-1 and HIF- 1 α in myocardial tissue were detected by qRT-PCR and Western blot. @*Results @# Compared with the control group， the pathological damage of myocardial tissue in CIH group was serious，the levels of left ventricular end diastolic diameter (LVEDD) ，left ventricular end systolic dimension (LVESD) and serum cTNI，CKMB，Mb and LDH signif- icantly increased (P＜0. 05) ，and the levels of ROS，MDA，IL-1 β , IL-6，TNF-α and the mRNA and protein levels of SENP-1 and HIF-1α in myocardial tissue also significantly increased (P ＜0. 05 ) ，while the levels of LVEF， LVFS，serum GSH and SOD significantly decreased (P ＜0. 05) ，and the SUMOylates level of HIF-1α protein in myocardial tissue also significantly decreased (P ＜0. 05 ) ．Compared with CIH group，AAV-shSENP-1 group had less myocardial pathological damage，the levels of LVEDD，LVESD and serum cTNI，CKMB，Mb and LDH signifi- cantly decreased (P＜0. 05) ，and the levels of ROS，MDA，IL-1 β, IL-6，TNF-α and the mRNA and protein levels of SENP-1 and HIF-1α in myocardial tissue also significantly decreased (P＜0. 05) ，the levels of LVEF，LVFS，serum GSH and SOD significantly increased (P＜0. 05) ，and the SUMOylates level of HIF-1α protein in myocardial tissue also significantly decreased (P＜0. 05) ． @*Conclusion @# Inhibition of SENP-1 expression can alleviate CIH induced myocarditis and oxidative stress in rats，improve myocardial injury and cardiac dysfunction，and its mechanism may be related to the improvement of HIF-1α SUMOylates level，thus inhibiting HIF-1α expression.
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Objective @# By observing the changes of interleukin-22 ( IL-22) ，signal transduction and transcriptional activator 3 (STAT3) ，fasting blood glucose ( FBG) and fasting insulin ( FINS) of rats under the circumstance of chronic intermittent hypoxia and reoxygenation，to explore the role of IL-22 / STAT3 pathway in insulin resistance in- duced by chronic intermittent hypoxia．@*Methods @#4 SD rats were randomly divided into control group (NC group) and intermittent hypoxia group ( CIH group) ，with 12 rats in each group．NC group was placed in normoxia environment for 12 weeks，while CIH group was first given intermittent hypoxia for 8 weeks and then resumed normoxia feeding until 12 weeks．FBG，FINS，IL-22 and p-STAT3 / STAT3 levels were measured at baseline，week 8 and week 12 in both groups，and insulin resistance index (HOMA-IR) was calculated．The differences between the two groups were compared. @*Results @#① There was no significant difference of the observation indexes between the two groups at baseline (P＞0. 05) ．At 8 weeks，the levels of FBG，FINS and HOMA-IR in CIH group were higher than those in NC group (P＜0. 05) ，and the levels of IL-22 were lower than those in NC group (P ＜0. 05) ．p-STAT3 / STAT3 showed a decreasing trend，but not statistically significant．At 4 weeks of reoxygenation，there were no significant differences in FBG，FINS，HOMA-IR and IL-22 levels between the two groups (P ＞0. 05 ) ．p-STAT3 / STAT3 in CIH group was significantly higher than that in NC group ( P ＜0. 05 ) . ② Spearman rank correlation analysis showed that HOMA-IR was negatively correlated with IL-22 and p-STAT3 / STAT3 ( all P ＜0. 05) ．@*Conclusion@#Chronic intermittent hypoxia can inhibit the expression of IL-22 / STAT3 signaling pathway，IL-22 / STAT3 signaling pathway may mediate insulin resistance induced by chronic intermittent hypoxia.
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Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.
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Objective:To investigate the effects of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine (Tempol) on the expressions of hypoxia inducible factor-1 α (HIF-1α)/vascular endothelial growth factor (VEGF) and lung development in premature neonatal rats under intermittent hypoxia (achieved by supplying a low concentration of oxygen).Methods:The intermittent hypoxia model was established.Caesarean section of rats was performed at 21 days of gestation when the fetal rats were estimated to be in labor.A total of 192 premature neonatal rats survived and were randomly divided into 6 groups according to random number table method: air control+ saline group, air control+ Tempol group, constant oxygen + saline group, constant oxygen + Tempol group, intermittent hypoxia + saline group, and intermittent hypoxia + Tempol group, 32 rats in each group.On the 7 th, 14 th and 21 st day of birth, the lung tissues of 8 neonatal preterm rats in each group were taken.Malondialdehyde (MDA) and total antioxidant capacity (TAOC) were detected by chemical analysis.The mRNA and protein levels of HIF-1α and VEGF were detected by real-time fluorescence quantitative PCR (qPCR) and immunohistochemistry, respectively.Another 8 neonatal rats in each group were taken for pulmonary function test on the 21 st day after birth. One- way ANOVA and SNK- q test were used for comparison among and between groups, respectively. Results:Compared with the constant oxygen + saline group, the intermittent hypoxia + saline group showed mild pulmonary septal thickening, increased MDA, decreased TAOC, elevated mRNA and protein expression levels of VEGF and HIF-1 α, and decreased lung function indexes.The differences were statistically significant (all P<0.05). Compared with the corresponding saline group, the intermittent hypoxia + Tempol group had decreased MDA and increased TAOC, and the differences were statistically significant at 14 d[MDA(3.09±0.45) nmol/(mg·pr) vs.4.02±0.30) nmol/(mg·pr), TAOC(3.13±0.31) U/(mg·pr) vs.(2.44±0.22) U/(mg·pr)]and 21 d[MDA(2.87±0.43) nmol/(mg·pr) vs.(4.47±0.56) nmol/(mg·pr), TAOC(3.47±0.35) U/(mg·pr) vs.(2.31±0.32) U/(mg·pr)] (all P<0.05). Compared with the corresponding saline group, the mRNA and protein expression of HIF-1 α and VEGF decreased in the intermittent hypoxia+ Tempol group, and the decrease in the mRNA expression of HIF-1 α was statistically significant at 14 d (2.11±0.60 vs.2.88±0.59) (all P<0.05). Lung function indexes, including tidal volume[(0.41 ± 0.01) mL vs.(0.36±0.02) mL], minute respiratory ventilation[(35.48 ± 2.95) mL vs.(30.62±2.27) mL], maximum expiratory flow[(2.19 ± 0.19) mL/s vs.(1.51±0.19) mL/s]and dynamic lung compliance[(2.65 ± 0.40) mL/cmH 2O vs.(1.83±0.34) mL/cmH 2O, 1 cmH 2O=0.098 kPa]increased (all P<0.05). Conclusions:Tempol can alleviate the lung injury induced by intermittent hypoxia under the intervention of a low concentration of oxygen to premature newborn rats and improve their lung function.
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Objective @#To investigate the role of endoplasmic reticulum stress in hepatic insulin resistance induced by intermittent hypoxia in rats．@*Methods @#Twenty-four SD rats were randomly divided into control group ( NC group) and intermittent hypoxia group ( CIH group) ．The NC group was placed in a normoxia environment for 12 weeks，and the CIH group was given intermittent hypoxia for 8 weeks，and then returned to normoxia until the 12th week．In both groups，fasting blood glucose (FBG) ，fasting insulin (FINS) ，and liver inositol-requiring enzyme- 1 α(IRE1 α) ，X-box binding protein 1s(XBP1s) ，forkhead box transcription factor O1 (FoxO1) ，activating transcription factor-6(ATF6) ，cAMP-response element binding protein( CREB) ，CREB-regulated transcription coacti- vator-2( CRTC2) ，double-stranded RNA-dependent protein kinase-like ER kinase ( PERK) ，eukaryotic initiation factor 2 α(eIF2 α) ，protein kinase B ( AKT) ，phosphoenolpyruvate carboxykinase ( PEPCK) ，glucose-6-phosphat- ase( G6Pase) mRNA were measured at baseline，week 8，and week 12 .@*Results @#There was no significant differ- ence in each observation index between the two groups at baseline ; at 8 weeks，the levels of FBG，FINS and the mRNA levels of IRE1α , XBP1s，ATF6，PERK，eIF2 α , PEPCK and G6Pase in the CIH group were higher than those in the NC group (P＜0. 05) ，while the mRNA levels of CREB，CRTC2 and AKT were lower than those in the NC group (P＜0. 05) ; at 12 weeks，there was no significant difference in each observation index between the two groups．Pearson correlation analysis showed(8th week of intermittent hypoxia group) : homeostasis model as- sessment-insulin resistance(HOMA-IR) was positively correlated with FoxO1，CREB，CRTC2 and PERK，eIF2 α mRNA levels (r = 0. 172，0. 595，0. 183，0. 702，0. 608 ; P＜0. 05) while it was negatively correlated with IRE1α , XBP1s，ATF6，AKT mRNA levels (r = －0. 422 ，－0. 327 ，－0. 309 ，－0. 399 ; P＜0. 05) ．@*Conclusion @#Intermittent hypoxia can lead to insulin resistance，and endoplasmic reticulum stress may mediate this effect.
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Objective:To systematically review the rehabilitation effects of moderate intermittent hypoxia on clinical related diseases. Methods:Literatures about rehabilitation effects of moderate intermittent hypoxia on clinical related diseases from 2004 to 2021 were searched in PubMed, ScienceDirect, CNKI and Wanfang databases using a systematic review method. Results:A total of 27 literatures were included, which focused on the effects on neural system, respiratory system, and cardiovascular diseases, as well as the regulation of metabolic and the improvement of exercise ability. Conclusion:Moderate intermittent hypoxia could improve the cognitive function, alleviate the symptoms of ischemic stroke, accelerate the recovery of spinal cord injury, resist depression and reduce blood pressure; regulate metabolism, improve aerobic capacity, enhance respiratory function and myocardial function. However, more researches are needed to make it clear that the standard on the duration of hypoxia within episodes, the number of hypoxia/reoxygenation cycles (episodes) per session every day, the pattern of presentation, and the cumulative duration of exposure.
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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
Subject(s)
Animals , Rats , Adiponectin/genetics , Hypoxia , Islets of Langerhans , Mitochondrial Dynamics , Rats, WistarABSTRACT
Objective To investigate the protective effects of astragaloside IV (AS IV) on chronic intermittent hypoxia (CIH) -induced cardiac injury. Methods Twenty-four male adult Sprague Dawley rats were randomly assigned to control, CIH, CIH+ASIV, and ASIV group, 6 rats in each group. Circular nitrogen and oxygen were filled to make oxygen concentration change between 9%-21% for the CIH treated rats. The exposure cycle was repeated every 3 minutes, 8 hours/ day for 35 days. ASIV was given by intragastric administration daily before intermittent hypoxia exposure in the CIH+ASIV group and AS IV group. The control group and CIH group were given normal saline of the same quantity. Echocardiography was used to analyse cardiac function. Myocardial structure was assessed by HE and wheat germ agglutinin staining. The apoptosis of cardiomyocytes was detected by TUNEL assay. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in heart were detected by commercial kits. Western blotting was used to evaluate the levels of Bcl-2, Bax, LC3, Beclinl, P62, and mammalian target of rapamycin (mTOR). Results In the CIH group, the left ventricular ejection fraction (LVEF) and left ventricular internal diameter at end-systole (LVIDs) were inhibited, the myocyte cells showed disordered arranged, enlarged diameters and higher apoptosis rate. The MDA content was significantly elevated and the SOD activity decreased in CIH group when compared with those of control. What's more, the expression level of Beclin 1 decreased while the P62 expression and the p-mTOR/mTOR ratio increased in the CIH group. Compared with the model group, the LVEF, LVIDs, SOD activity, LC3 H / I ratio, and Beclinl expression of rats in the CIH + AS IV group increased. The cardiomyocytes in the rats of CIH + ASIV group showed normal arrangement and diameters. The apoptosis rate, MDA content, P62 expression and the p-mTOR/mTOR ratio decreased in the CIH+ASIV group when compared with the CIH group. Conclusion AS IV can alleviate CIH-induced cardiac injury by promoting autophagy via mTOR.
ABSTRACT
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.
Subject(s)
Humans , Male , Altitude Sickness , Miners , Sleep Quality , Melatonin/blood , Oximetry , Chile , Oxygen Saturation , HypoxiaABSTRACT
Objective To observe the expression and localization of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in rat adrenal gland and to detect the effect of cyclic intermittent hypoxia (CIH) on the expression of BACE1. Methods The expression and localization of BACE1 in rat adrenal gland were detected by Western blotting and immunohistochemistry. Sixteen male Sprague-Dawley (SD) rats were randomly divided into two groups: control group and CIH group, 8 rats in each group. The protein levels of BACE1 and tyrosine hydroxylase (TH) in rat adrenal medulla were detected by Western blotting after CIH 2 weeks treatment. Results BACE1 was mainly localized in rat adrenal medullary nerve fibers. Compared with the control group, BACE1 protein level decreased and TH protein level increased in the adrenal medulla in the CIH group. Conclusion BACE1 is located in rat adrenal medullary nerve fibers. The decreased level of BACE1 may participate in slowing down the excessive enhancement of sympathetic activity induced by CIH.