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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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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 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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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
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.
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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 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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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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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 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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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.
ABSTRACT
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.